Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Translations
    • Topics A-Z
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Translations
    • Topics A-Z
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Articles
  • Issues

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Genetics
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues

Share

December 2021; 7 (6) ArticleOpen Access

Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants in GPAA1

Alison M.R. Castle, Smrithi Salian, Haim Bassan, Efrat Sofrin-Drucker, Raffaella Cusmai, Kristin C. Herman, Delphine Heron, View ORCID ProfileBoris Keren, Devon L. Johnstone, Wendy Mears, Susanne Morlot, Thi Tuyet Mai Nguyen, Rachel Rock, Elliot Stolerman, Julia Russo, William Boyce Burns, Julie R. Jones, Valentina Serpieri, Hannah Wallaschek, Ginevra Zanni, David A. Dyment, View ORCID ProfilePhilippe M. Campeau
First published October 21, 2021, DOI: https://doi.org/10.1212/NXG.0000000000000631
Alison M.R. Castle
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: acastle@cheo.on.ca
Smrithi Salian
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: smriti.smz@gmail.com
Haim Bassan
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: haim.bassan@gmail.com
Efrat Sofrin-Drucker
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: efratsof@clalit.org.il
Raffaella Cusmai
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: raffaella.cusmai@opbg.net
Kristin C. Herman
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kcherman@ucdavis.edu
Delphine Heron
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: delphine.heron@aphp.fr
Boris Keren
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Boris Keren
  • For correspondence: boris.keren@aphp.fr
Devon L. Johnstone
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: devon.johnstone@uottawa.ca
Wendy Mears
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wmears@cheo.on.ca
Susanne Morlot
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: morlot.susanne@mh-hannover.de
Thi Tuyet Mai Nguyen
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ducmai.nguyen@gmail.com
Rachel Rock
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: rokrachel9@gmail.com
Elliot Stolerman
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: estolerman@ggc.org
Julia Russo
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jrusso@ambrygen.com
William Boyce Burns
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: william.burns@nationwidechildrens.org
Julie R. Jones
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: juliejones@ggc.org
Valentina Serpieri
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: valentina.serpieri01@universitadipavia.it
Hannah Wallaschek
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wallaschek.hannah@mh-hannover.de
Ginevra Zanni
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ginevra.zanni@opbg.net
David A. Dyment
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ddyment@cheo.on.ca
Philippe M. Campeau
From the Department of Genetics (A.M.R.C., D.A.D.), Children's Hospital of Eastern Ontario, Ottawa; CHU Sainte Justine Research Centre (S.S., T.T.M.N., P.M.C.), Université de Montréal, Quebec, Canada; Pediatric Neurology & Development Center (H.B.), Shamir (Assaf Harofeh) Medical Center, Zerifin, Tel Aviv University; Pediatric Genetics Clinic (E.S.-D.), Schneider Children's Medical Centre, Petach Tikya, Tel Aviv University, Israel; Unit of Neurophysiology, Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; Section of Medical Genomics (K.C.H.), Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, Sacramento; APHP (B.K.), Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France; APHP Sorbonne-Université (D.H.), UF Génétique Médicale, Hôpitaux Pitié-Salpêtrière et Trousseau, Centre de Référence “déficiences intellectuelles de causes rares”, Paris, France; Children's Hospital of Eastern Ontario Research Institute (D.L.J., W. M., D.A.D.), Ottawa, Canada; Department of Human Genetics (S.M., H.W.), Hannover Medical School, Germany; Biochemical Diseases (R.R.), BC Children's Hospital, Vancouver, British Columbia, Canada; Greenwood Genetic Center (E.S., J.R., W.B.B., J.R.J.), SC; Department of Molecular Medicine (V.S.), University of Pavia; Neurogenetics Research Center (V.S.), IRCCS Mondino Foundation, Pavia; Unit of Neuromuscular and Neurodegenerative Disorders (G.Z.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy; and Medical Genetics Division (P.M.C.), Department of Pediatrics, Sainte-Justine University Hospital Centre, Montreal, Quebec, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Philippe M. Campeau
Full PDF
Citation
Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants in GPAA1
Alison M.R. Castle, Smrithi Salian, Haim Bassan, Efrat Sofrin-Drucker, Raffaella Cusmai, Kristin C. Herman, Delphine Heron, Boris Keren, Devon L. Johnstone, Wendy Mears, Susanne Morlot, Thi Tuyet Mai Nguyen, Rachel Rock, Elliot Stolerman, Julia Russo, William Boyce Burns, Julie R. Jones, Valentina Serpieri, Hannah Wallaschek, Ginevra Zanni, David A. Dyment, Philippe M. Campeau
Neurol Genet Dec 2021, 7 (6) e631; DOI: 10.1212/NXG.0000000000000631

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
478

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Background and Objectives To expand the clinical knowledge of GPAA1-related glycosylphosphatidylinositol (GPI) deficiency.

Methods An international case series of 7 patients with biallelic GPAA1 variants were identified. Clinical, biochemical, and neuroimaging data were collected for comparison. Where possible, GPI-anchored proteins were assessed using flow cytometry.

Results Ten novel variants were identified in 7 patients. Flow cytometry samples of 3 available patients confirmed deficiency of several GPI-anchored proteins on leukocytes. Extensive phenotypic information was available for each patient. The majority experienced developmental delay, seizures, and hypotonia. Neuroimaging revealed cerebellar anomalies in the majority of the patients. Alkaline phosphatase was within the normal range in 5 individuals and low in 1 individual, as has been noted in other transamidase defects. We notably describe individuals either less affected or older than the ones published previously.

Discussion Clinical features of the cases reported broaden the spectrum of the known phenotype of GPAA1-related GPI deficiency, while outlining the importance of using functional studies such as flow cytometry to aid in variant classification.

Glossary

AP=
anchored protein;
ALP=
alkaline phosphatase;
FLAER=
fluorescein-labeled proaerolysin;
GPI=
glycosylphosphatidylinositol;
WES=
whole-exome sequencing

The glycosylphosphatidylinositol (GPI) anchor pathway plays an essential role in posttranslational modification of a variety of proteins integral to cell signaling and function.1 Proteins targeted for GPI modification are captured in the cytoplasm and translocated to the endoplasmic reticulum where they acquire the GPI moiety. They are then transferred to the Golgi apparatus for remodeling and maturation of the GPI-anchored protein (GPI-AP), before being transferred to the plasma membrane. These proteins localize to numerous cell types and play integral roles in a variety of cellular processes. Examples of GPI-APs include Fcγ receptors such as CD16, regulators of the complement pathway such as CD59, and cell surface enzymes such as alkaline phosphatase (ALP).2,3 In the nervous system, GPI-APs play an vital role in axon growth, axon regeneration, synapse formation, and synaptic plasticity.4 Dysfunction of neural GPI-APs has been linked to a variety of neurologic diseases including autism spectrum disorder, schizophrenia, and MS.4

Numerous neurodevelopmental disorders have been associated with variants in genes involved in the biosynthesis of GPIs. Inherited GPI deficiency disorders, also referred to as glycosylphosphatidylinositol biosynthesis defects or GPIBDs, are a group of autosomal recessive or X-linked recessive syndromic intellectual disability disorders. In 2006, the first cases of inherited GPI deficiency were documented, with the descriptions of patients with thrombosis and seizures who were found to have biallelic pathogenic variants in PIGM.5 More recently, extensive phenotypic descriptions of patients with variations in several genes (e.g., PIGN, PIGT, PIGY, and PIGK) in the pathway have been published.6,-,9 GPAA1 encodes a subunit of the GPI-lipid anchor transamidase complex.10 Its role in human cancers has been described since 200611; however, its delineation as a cause of syndromic intellectual disability is more recent.2

A cohort of 10 patients from 5 families are the only reported individuals affected by GPAA1-related GPI deficiency (OMIM 617810), also known as GPI biosynthesis defect 15.2 Patients with pathogenic variants in GPAA1 have developmental delay, hypotonia, seizures, cerebellar atrophy, dysarthria, dysmetria, ataxia, osteopenia, and variable dysmorphic features.2 In this study, we describe and broaden the clinical and biochemical variability associated with GPAA1-related GPI deficiency in an additional 7 families.

Methods

Seven individuals from unrelated families with biallelic GPAA1 variants (GenBank: NM_003801.3) are included in this case series. Individuals were identified from international centers through direct communication between clinicians and the authors of the original GPAA1 case series. Whole-exome sequencing (WES) was performed on both research and clinical bases according to protocols laid out by the respective laboratories (Supplemental Data, links.lww.com/NXG/A479). Developmental assessments were performed by pediatricians, pediatric neurologists, and developmental pediatricians. Seizure and EEG classification were performed by neurologists or pediatric neurologists. Dysmorphology examinations were performed by medical geneticists.

Standard Protocol Approvals, Registrations, and Patient Consents

Informed consent including consent for publication of photographs, imaging, and clinical information was obtained from each family in accordance with guidelines established by the institutional review boards at their primary site of care. CARE reporting guidelines were followed while preparing this article.12

Fluorescence-Activated Cell Sorting Analysis

Blood samples collected from 3 of the 7 patients (II, III, and VII), 3 different healthy controls, and the father of an affected individual were subjected to flow cytometry to assess the effect of GPAA1 variants on the cell surface GPI-APs on granulocytes. Blood samples were stained for an hour on ice with phycoerythrin-conjugated anti-human CD16 (BioLegend), fluorescein-labeled proaerolysin (FLAER)-Alexa 448 (Cedarlane), and fluorescein isothiocyanate-conjugated mouse anti-human CD55 or CD59 (BD PharMingen). Samples were treated with fluorescence-activated cell sorting Lysing Solution (BD Biosciences) before flow cytometry analysis (BD FACSCanto II system (BD Biosciences). FlowJo software (v9.5.3, Tommy Digital) was used to analyze the data.

Data Availability

Original data can be made available on request; genetic data or clinical data sharing may be subject to privacy restrictions.

Results

Clinical presentations of the 7 patients are outlined in Table 1. Patients were 43% male (3/7). The age of the patients was variable, ranging from 6 weeks to 3 years at the time of diagnosis. Symptom onset was generally between birth and 4 months, when hypotonia was noted. All patients presented with developmental delays or intellectual disability of varying severity. Epilepsy was seen in 6/7 individuals, with the first seizure occurring between 8 months to 3 years. Numerous seizure types were observed, with 4 patients experiencing febrile seizures, 2 patients with absence seizures, 3 patients with bilateral tonic-clonic seizures, 2 patients with myoclonic jerks, and 1 patient experiencing epileptic spasms. Only 1 patient, aged 22 months, had not experienced a seizure. EEG data were available for 5 patients and showed variable findings, including normal, nonspecific changes, spike/polyspike discharges, multifocal spike and wave, and slow wave epileptiform discharges; no common EEG pattern was seen. Patients were maintained on a variety of antiepileptic medications (Supplemental Data, links.lww.com/NXG/A479).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 1

Key Clinical Features of Previously Reported and New Patients

Six of 7 patients were described as hypotonic and 2 demonstrated spasticity. In all patients with hypotonia, it was either present at birth or noted before 4 months of age. Cerebellar atrophy was seen in 3/6 patients (Figure 1 and eFigure 2, links.lww.com/NXG/A479). It was progressive in 1 patient (eFigure 1), with imaging at 7 months of age demonstrating benign enlargement of the subarachnoid space of infancy with a normal cerebellum. Imaging was repeated at age 2 years and demonstrated mild diffuse and symmetrical brain atrophy with progression in the cerebellum. The second patient did not have neuroimaging until age 21 years; this demonstrated cerebellar atrophy, which has been stable on repeat imaging at ages 25 and 29 years. The third patient with cerebellar atrophy has not been assessed with serial MRIs. In 2 of these individuals, additional abnormalities were noted, including slightly delayed myelination and mild thinning or hypoplasia of the corpus callosum.

Figure 1
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1 Sagittal T1 Images From Patients With GPAA1-Related Glycosylphosphatidylinositol Deficiency

(A) Neuroimaging from patient I, taken at age 21 years. Note the cerebellar atrophy with prominent folia. (B) Sagittal T1 MRIs from patient II, in whom biallelic GPAA1 variants were found incidentally on exome sequencing. The cerebellum is normal in this patient. (C) Neuroimaging from patient III from 2018. Although her initial MRI did not report cerebellar hypoplasia/atrophy, subsequent cerebellar atrophy was noted on this follow-up imaging (shown) performed at age 2 years. Slightly delayed myelination and mild thinning of the corpus callosum was also identified. (D) Sagittal T1 MRI images from patient V, showing severe vermian hypoplasia/atrophy and thinning of the superior cerebellar peduncle and bilateral cerebellar hemisphere atrophy. The corpus callosum was also noted to be hypoplastic.

Associated features included nystagmus in 2 patients, dysarthria in 1 patient (not assessed in 4 patients given their age or language capacity), dysmetria in 1 patient, and ataxia in 3 patients. Osteopenia was present in 1 patient with a bone density Z score of −2.3; however, it was not assessed in 5 patients in the cohort. Plasma ALP levels were within the normal range in 5 patients and low in 1 patient. Variable dysmorphic features were described, with common descriptions including prominent forehead and a tented upper lip. Three patients were not dysmorphic.

We identified novel variants in GPAA1 in all cases (Table 2, Figure 2). Variants were identified on clinical WES in 5 patients and research WES in the remaining 2 patients. Indications for testing included developmental delay, hypotonia, seizures, and ataxia (Supplemental Data, links.lww.com/NXG/A479). In total, there were 10 new variants identified in the 7 patients, as 3 patients were homozygous for GPAA1 variants, and 2 unrelated patients were observed to carry the same variant. Seven variants were missense: c.164T>C (p.Met55Thr), c.1049T>G (p.Leu350Arg), c.917A>G (p.His306Arg), c.1559T>G (p.Leu520Arg), c.947C>T (p.Ala316Val), c.1831T>C (p.Trp611Arg), and c.149T>A (p.Met50Lys). Three variants were deletions resulting in frameshifts: c.1233_1239del (p.Pro412Tyrfs*19), c.1477_1478del (p.Arg493Glyfs*152), and c.619delA (p.Met207Cysfs*21). No nonsense variants were identified in this cohort of patients (eTable 1).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 2

Genetic Description of GPAA1 Variants

Figure 2
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2 Variant Localization and Residue Conservation

(A) Schematic representation of missense and frameshift GPAA1 variants, with previously reported variants indicated in blue, and novel variants indicated in red. (B) Amino acid conservation in vertebrates. (C) Three-dimensional modeling of the luminal domain of GPAA1, which spans residues 66–348.35 Shown in red are 2 missense variants within this domain.

FLAER staining is used as a marker of total GPI-APs,2,13 and specific GPI-APs such as CD16 can be quantified via flow cytometry. To assess the effect of the GPAA1 variants on the biosynthesis of GPI-APs, flow cytometry analyses were performed on blood samples from 3 patients. On the granulocytes of patients II, III, and VII, there was a 47%, 37%, and 12% decrease in the CD16 level compared with healthy controls, respectively (Figure 3). CD55, CD59, and total GPI-AP levels in these individuals showed slightly decreased or no change in the levels compared with healthy controls. The father of an affected parent, who carries a frameshift variant in GPAA1, did not have abnormalities on flow cytometry (eFigure 3, links.lww.com/NXG/A479).

Figure 3
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3 Flow Cytometry Analysis of CD16 on Granulocytes in patients II, III, and VII Compared With a Healthy Control

The histograms are representatives of at least 2 separate experiments using 3 different controls. There was a 47%, 37%, and 12% decrease in the CD16 level on the granulocytes of patients II, III, and VII, respectively, compared with controls. In addition, there was no significant reduction in glycosylphosphatidylinositol-anchored protein levels in the father of patient VII, who carries a frameshift variant. PE-A = phycoerythrin area.

Discussion

The present report of 7 new cases of GPAA1-related GPI deficiency both affirms and expands on the phenotype previously described.2 The most common features seen in the series are seizures, developmental delay, and hypotonia.

Variability in this cohort was marked. Patient II had a considerably milder clinical phenotype compared with the other patients in both this and the previously reported cohort. At age 22 months, the patient had developmental delay, most notably in motor milestone acquisition and adaptive development. Her problem solving, receptive language, and socioemotional function was slightly below expected for her age. She has no seizures, hypotonia, or cerebellar atrophy (Figure 1). In all other individuals, hypotonia presented within the first 4 months of life. Seizures are more variable in onset; however, most patients in this case series had onset of epilepsy before 22 months (Supplemental Data, links.lww.com/NXG/A479). Her main medical concern was early onset inflammatory bowel disease; GPAA1 variants were considered incidental findings on exome sequencing. However, flow cytometry assays support the pathogenicity of the variants by demonstrating reduction in CD16 in granulocytes. Similar to other patients in this series, there was no decrease in other markers. Taken together, her clinical and biochemical findings could suggest a milder variant, and she will continue to be monitored for disease manifestations.

Patient I is, to date, the oldest individual reported with GPAA1 deficiency. His clinical presentation includes many cardinal features of the disorder, including neonatal hypotonia, generalized epilepsy with multiple seizure types, stable global cerebellar atrophy (eFigure 2, links.lww.com/NXG/A479), osteopenia, and normal ALP. He exhibits several cerebellar symptoms including ataxia, dysarthria, and dysmetria. He has impairments in fine motor skills and is unable to stand, read, or write, however he does eat and undress independently.

Clinical features reported in these patients reflect what was described in the first cohort of patients with GPAA1-related GPI deficiency.2 Developmental delay of variable severity was universal in both cohorts. Two patients are nonverbal; all others had delayed language acquisition and ongoing impaired communication. All patients had delayed motor development: 1 patient cannot sit independently; others achieved this milestone between 11 months and 4 years. Ambulation is present in 1 patient, achieved at 6 years; however, the majority of patients in the cohort remain below age 6 years and may ambulate in the future (Supplemental Data, links.lww.com/NXG/A479). Hypotonia and seizures were also seen in comparable frequencies (Table 1). No common seizure type or EEG pattern was identified. Cerebellar atrophy was seen less frequently, with only 50% of patients demonstrating this finding on neuroimaging. Other intracranial abnormalities are seen in some individuals, including delayed myelination, mild thinning of the corpus callosum, and hypoplasia of the corpus callosum. Similar anomalies have been described in patients with other GPIBDs, reflective of the importance of GPI-APs in neural development.4,14,-,16 Flow cytometry identified decreased levels of only CD16 compared with previously reported patients with decreased CD16, CD59, and total GPI-AP.2 A characteristic flow cytometry profile in granulocytes has been described for individuals with PIGU and PIGT variants.16 GPAA1 deficiency does not demonstrate a characteristic pattern; however, measuring GPI-APs through flow cytometry remains a mechanism by which functional consequences of GPAA1 variants can be investigated.

Similar to the previous cohort, no homozygous loss-of-function variants were identified in this series of patients. This is suggestive of the importance of having residual functional gene product, a hypothesis supported by the fact that this pathway is conserved in all eukaryotes.17 All variants were novel; however, a recurrent variant was identified in 2 unrelated individuals. The p.Ala316Val substitution was found in an individual of Kurdish Turk descent in a homozygous state and in an unrelated Israeli individual with compound heterozygous variants. Both patients have severe global developmental delay; however, physical anomalies vary between the 2, including the presence of cerebellar atrophy in only the patient with compound heterozygous variants. That patient also has a more severe epileptic disorder, with poor seizure control despite multiple medications (Supplemental Data, links.lww.com/NXG/A479).

Osteopenia was a universal finding in the first cohort of patients identified by Nguyen et al. in 2017. Only 2 patients in this series have been assessed with dual-energy X-ray absorptiometry scans, with osteopenia present in 1. With ongoing surveillance of individuals with GPI-related disorders and osteopenia, it will hopefully be determined if its presence leads to adverse health outcomes. Given the independent association of osteopenia and osteoporosis with epilepsy, antiepileptic use, and decreased mobility, one may anticipate patients with GPAA1 deficiency are at risk of fractures, and bone health should be promoted and monitored.18 At least 1 individual with PIGT-related GPI deficiency has had fractures due to decreased bone mineral density.19

Osteopenia and osteoporosis are hypothesized to be secondary to decreased alkaline phosphatase (ALP) expression on the surface of osteoblasts, impairing their function and leading to decreased bone formation and therefore bone mineral density. Hyperphosphatasia is a consequence of deficient ALP membrane attachment. ALP tends to be elevated when proteins in later steps of the GPI pathway are dysfunctional, as the GPI anchor cannot be appropriately attached to the protein. The cell is left with soluble ALP that is then released into the serum.3 The GPI-transamidase complex, which includes proteins encoded by GPAA1, PIGK, PIGS, PIGT, and PIGU, mediates the attachment of the GPI anchor to targeted proteins.20 None of the patients described in the literature with pathogenic variants in GPI-transamidase complex genes have elevated ALP.2,14,21,22 In fact, several patients with PIGT and PIGK pathogenic variants have decreased alkaline phosphatase.7,9 Our cohort of patients is consistent with this pattern, as none had elevated ALP or hyperphosphatasia, but 1 patient had a decreased ALP.

About half of patients with GPI-related disorders have abnormalities on neuroimaging including hypoplasia of the corpus callosum and white matter loss.14 Cerebellar hypoplasia and atrophy is noted in 10 different disorders (PIGA, PIGL, PIGN, PIGO, PIGG, PIGK, PIGS, PIGT, GPAA1, and PGAP1).2,6,9,14,23,-,28 In the original cohort of patients with GPAA1 deficiency, 9 of 10 patients had cerebellar anomalies; the 1 patient without cerebellar atrophy was only 1 year of age and perhaps too young to have developed the finding. Acquired cerebellar atrophy was noted in patient III of this cohort. Neuroimaging at 7 months showed a normal cerebellum; however, a repeat MRI at 2 years confirmed diffuse brain atrophy with the most striking progression in the cerebellum (see eFigure 1, links.lww.com/NXG/A479). Acquired, rather than congenital, cerebellar abnormalities may prove to be a common feature of the disorder, not yet fully appreciated as most children have MRI scans after onset of clinical manifestations caused by the presence of cerebellar atrophy. However, symptoms of nystagmus, dysarthria, and dysmetria were not congruent with the presence of cerebellar anomalies, suggesting that neuroimaging should be considered even in the absence of these signs and symptoms.

No patients had vascular anomalies including venous or capillary malformations. It was recently suggested that heterozygous loss-of-function variants in GPAA1 are associated with these anomalies.29 Data from patient cohorts published to date suggest GPAA1-related disorders are inherited in a recessive manner, and parents who carry loss-of-function variants in GPAA1 have not been found to have any health effects including vascular anomalies. As more patients are identified with biallelic GPAA1 variants, family studies to assess the dermatologic and vascular phenotypes in heterozygotes may provide clarity regarding this relationship. Of interest, that same publication showed that GPAA1 knock-out models of zebrafish embryos develop numerous differences, including shortened length, back hyperextension, and smaller eyes, suggesting that GPAA1 plays a critical role in embryonic development. More studies will be needed to extrapolate the relevance of these findings to affected patients.

At present, treatments for GPI-related disorders are limited and primarily focused on seizure control. There is a case report of an individual with GPI deficiency due to variants in PIGM whose severe seizures were treated successfully with the histone deacetylase inhibitor sodium butyrate.30,31 However, this is likely not a feasible treatment for all GPI-related disorders, as the patient's specific pathogenic variant was in the PIGM promotor and led to decreased acetylation and therefore decreased gene expression. Two brothers with early infantile epileptic encephalopathy due to PIGA pathogenic variants had resolution of their seizures after initiation of the ketogenic diet, but the mechanism for this has not been fully elucidated.32 Two patients in this cohort are currently or were previously managed on the ketogenic diet. In at least one of the patients, a partial but significant reduction in seizure frequency was observed. Previous case reports have discussed the efficacy of pyridoxine (B6) in seizure management in hyperphosphatasia with intellectual disability syndromes (caused by variants in PIGV, PIGY, PIGO, PGAP2, PIGW, and PGAP3).21,33,34 ALP allows pyridoxal phosphate to cross the blood-brain barrier; thus, deficiency on cellular surfaces due to impaired GPI protein anchoring may lead to cerebral B6 deficiency, which can be addressed with B6 supplementation. Three of 7 patients in this report are using B6 as a part of their treatment regimen for seizure control. In 2 of these patients, control is suboptimal with ongoing breakthrough seizures; the third patient has well-controlled epilepsy. B6 is not felt to have contributed significantly to seizure control.

This cohort of patients supports and expands on the previously described phenotype, as it includes individuals who are either older or more mildly affected than those previously described. This will allow clinicians to begin to appreciate what long-term outcomes may look like for their affected patients. Functional assays such as flow cytometry aid in identifying true pathogenic variants causing decreased GPI-anchored protein expression vs variants of no functional significance, helping establish a library of causative variants. The quantitative nature of these assays in conjunction with access to clear clinical information may assist scientists in establishing a clear genotype-phenotype correlation. As is often the case in the era of next-generation sequencing, the full spectrum of GPAA1-related disorders will continue to evolve as additional patients are identified and characterized.

Study Funding

No targeted funding reported.

Disclosure

The authors report no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.

Acknowledgment

The authors thank the patients and families. They also thank the various research consortiums, including the Care4Rare Research Consortium, that aided in the identification of variants in patients. G. Zanni is a member of the European Reference Network for Rare Neurological Diseases, Project ID no 739510. The authors thank Enza Maria Valente (Rome, Italy) for her assistance in molecular analysis.

Appendix Authors

Table

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.

  • The Article Processing Charge was funded by the authors.

  • Received March 28, 2021.
  • Accepted in final form August 9, 2021.
  • Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

References

  1. 1.↵
    1. Kinoshita T
    . Biosynthesis and biology of mammalian GPI-anchored proteins. Open Biol. 2020;10(3):190290.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Nguyen TTM,
    2. Murakami Y,
    3. Sheridan E, et al
    . Mutations in GPAA1, encoding a GPI transamidase complex protein, cause developmental delay, epilepsy, cerebellar atrophy, and osteopenia. Am J Hum Genet. 2017;101(5):856-865.
    OpenUrlCrossRef
  3. 3.↵
    1. Murakami Y,
    2. Kanzawa N,
    3. Saito K, et al
    . Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome. J Biol Chem. 2012;287(9):6318-6325.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Um JW,
    2. Ko J
    . Neural glycosylphosphatidylinositol-anchored proteins in synaptic specification. Trends Cel Biol. 2017;27(12):931-945.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Almeida AM,
    2. Murakami Y,
    3. Layton DM, et al
    . Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiency. Nat Med. 2006;12(7):846-851.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Ohba C,
    2. Okamoto N,
    3. Murakami Y, et al
    . PIGN mutations cause congenital anomalies, developmental delay, hypotonia, epilepsy, and progressive cerebellar atrophy. Neurogenetics. 2014;15(2):85-92.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Kvarnung M,
    2. Nilsson D,
    3. Lindstrand A, et al
    . A novel intellectual disability syndrome caused by GPI anchor deficiency due to homozygous mutations in PIGT. J Med Genet. 2013;50(8):521-528.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Ilkovski B,
    2. Pagnamenta AT,
    3. O'Grady GL, et al
    . Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies. Hum Mol Genet. 2015;24(21):6146-6159.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Nguyen TTM,
    2. Murakami Y,
    3. Mobilio S, et al
    . Bi-allelic variants in the GPI transamidase subunit PIGK cause a neurodevelopmental syndrome with hypotonia, cerebellar atrophy, and epilepsy. Am J Hum Genet. 2020;106(4):484-495.
    OpenUrlCrossRef
  10. 10.↵
    1. Hamburger D,
    2. Egerton M,
    3. Riezman H
    . Yeast Gaa1p is required for attachment of a completed GPI anchor onto proteins. J Cel Biol. 1995;129(3):629-639.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Wu G,
    2. Guo Z,
    3. Chatterjee A, et al
    . Overexpression of glycosylphosphatidylinositol (GPI) transamidase subunits phosphatidylinositol glycan class T and/or GPI anchor attachment 1 induces tumorigenesis and contributes to invasion in human breast cancer. Cancer Res. 2006;66(20):9829-9836.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Gagnier JJ,
    2. Kienle G,
    3. Altman DG,
    4. Moher D,
    5. Sox H,
    6. Riley D
    . The CARE guidelines: consensus-based clinical case report guideline development. J Clin Epidemiol. 2014;67(1):46-51.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Pu JJ,
    2. Brodsky RA
    . Paroxysmal nocturnal hemoglobinuria from bench to bedside. Clin Transl Sci. 2011;4(3):219-224.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Bellai-Dussault K,
    2. Nguyen TTM,
    3. Baratang NV,
    4. Jimenez-Cruz DA,
    5. Campeau PM
    . Clinical variability in inherited glycosylphosphatidylinositol deficiency disorders. Clin Genet. 2019;95(1):112-121.
    OpenUrlCrossRef
  15. 15.↵
    1. Vetro A,
    2. Pisano T,
    3. Chiaro S, et al
    . Early infantile epileptic-dyskinetic encephalopathy due to biallelic PIGP mutations. Neurol Genet. 2020;6(1):e387.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Knaus A,
    2. Pantel JT,
    3. Pendziwiat M, et al
    . Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis. Genome Med. 2018;10(1):3-13.
    OpenUrl
  17. 17.↵
    1. Orlean P,
    2. Menon AK
    . GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids. J Lipid Res. 2007;48(5):993-1011.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Diemar SS,
    2. Sejling AS,
    3. Eiken P,
    4. Andersen NB,
    5. Jørgensen NR
    . An explorative literature review of the multifactorial causes of osteoporosis in epilepsy. Epilepsy Behav. 2019;100(Pt A):106511.
    OpenUrl
  19. 19.↵
    1. Nakashima M,
    2. Kashii H,
    3. Murakami Y, et al
    . Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3. Neurogenetics. 2014;15(3):193-200.
    OpenUrl
  20. 20.↵
    1. Kinoshita T
    . Biosynthesis and deficiencies of glycosylphosphatidylinositol. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90(4):130-143.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Nguyen TTM,
    2. Murakami Y,
    3. Wigby KM, et al
    . Mutations in PIGS, encoding a GPI transamidase, cause a neurological syndrome ranging from fetal akinesia to epileptic encephalopathy. Am J Hum Genet. 2018;103(4):602-611.
    OpenUrlCrossRef
  22. 22.↵
    1. Knaus A,
    2. Kortüm F,
    3. Kleefstra T, et al
    . Mutations in PIGU impair the function of the GPI transamidase complex, causing severe intellectual disability, epilepsy, and brain anomalies. Am J Hum Genet. 2019;105(2):395-402.
    OpenUrlCrossRef
  23. 23.↵
    1. Pagnamenta AT,
    2. Murakami Y,
    3. Taylor JM, et al
    . Analysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders. Eur J Hum Genet. 2017;25(6):669-679.
    OpenUrl
  24. 24.↵
    1. van der Crabben SN,
    2. Harakalova M,
    3. Brilstra EH, et al.
    Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities. Am J Med Genet A. 2014;164(1):29-35.
    OpenUrlCrossRef
  25. 25.↵
    1. Zhao JJ,
    2. Halvardson J,
    3. Knaus A, et al
    . Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function. Hum Mutat. 2017;38(10):1394-1401.
    OpenUrlCrossRef
  26. 26.↵
    1. Fujiwara I,
    2. Murakami Y,
    3. Niihori T, et al
    . Mutations in PIGL in a patient with Mabry syndrome. Am J Med Genet A. 2015;167A(4):777-785.
    OpenUrlCrossRef
  27. 27.↵
    1. Kettwig M,
    2. Elpeleg O,
    3. Wegener E, et al
    . Compound heterozygous variants in PGAP1 causing severe psychomotor retardation, brain atrophy, recurrent apneas and delayed myelination: a case report and literature review. BMC Neurol. 2016;16(1):74-77.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Makrythanasis P,
    2. Kato M,
    3. Zaki MS, et al
    . Pathogenic variants in PIGG cause intellectual disability with seizures and hypotonia. Am J Hum Genet. 2016;98(4):615-626.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Li Y,
    2. Yang L,
    3. Yang J, et al.
    A novel variant in GPAA1, encoding a GPI transamidase complex protein, causes inherited vascular anomalies with various phenotypes. Hum Genet. 2020;1390(12):1499-1511.
    OpenUrl
  30. 30.↵
    1. Almeida AM,
    2. Murakami Y,
    3. Baker A, et al
    . Targeted therapy for inherited GPI deficiency. N Engl J Med. 2007;356(16):1641-1647.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Almeida A,
    2. Layton M,
    3. Karadimitris A
    . Inherited glycosylphosphatidyl inositol deficiency: a treatable CDG. Biochim Biophys Acta. 2009;1792(9):874-880.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Joshi C,
    2. Kolbe DL,
    3. Mansilla MA,
    4. Mason S,
    5. Smith RJH,
    6. Campbell CA
    . Ketogenic diet—a novel treatment for early epileptic encephalopathy due to PIGA deficiency. Brain Dev. 2016;38(9):848-851.
    OpenUrl
  33. 33.↵
    1. Thompson MD,
    2. Killoran A,
    3. Percy ME,
    4. Nezarati M,
    5. Cole DEC,
    6. Hwang PA
    . Hyperphosphatasia with neurologic deficit: a pyridoxine-responsive seizure disorder? Pediatr Neurol. 2006;34(4):303-307.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Kuki I,
    2. Takahashi Y,
    3. Okazaki S, et al
    . Vitamin B6-responsive epilepsy due to inherited GPI deficiency. Neurology. 2013;81(16):1467-1469.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Su CT
    . Structural modelling of the lumenal domain of human GPAA1, the metallo-peptide synthetase subunit of the transamidase complex, reveals zinc-binding mode and two flaps surrounding the active site, preprint.

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study Funding
    • Disclosure
    • Acknowledgment
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

SARS-CoV-2 Vaccination Safety in Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Multifocal Motor Neuropathy

Dr. Jeffrey Allen and Dr. Nicholas Purcell

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • All Genetics
  • Developmental disorders

Alert Me

  • Alert me when eletters are published
Neurology Genetics: 9 (2)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Genetics | Online ISSN: 2376-7839

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise