WGS and RNA Studies Diagnose Noncoding DMD Variants in Males With High Creatine Kinase
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Article Information
- Received May 1, 2020
- Accepted in final form November 19, 2020
- First Published January 29, 2021.
Author Disclosures
- Leigh B. Waddell, PhD (leigh.waddell{at}health.nsw.gov.au),
- Samantha J. Bryen, BSc (Hons) (samantha.bryen{at}health.nsw.gov.au),
- Beryl B. Cummings, PhD (berylc{at}broadinstitute.org),
- Adam Bournazos, BSc (Hons) (adam.bournazos{at}health.nsw.gov.au),
- Frances J. Evesson, PhD (frances.evesson{at}health.nsw.gov.au),
- Himanshu Joshi, B Software Engineering, B Business (Finance) (himanshu.joshi{at}sydney.edu.au),
- Jamie L. Marshall, PhD (jmarshal{at}broadinstitute.org),
- Taru Tukiainen, PhD (taru.tukiainen{at}gmail.com),
- Elise Valkanas, BA (Biology) (valkanas{at}broadinstitute.org),
- Ben Weisburd, BS (Computer Sc) (weisburd{at}broadinstitute.org),
- Simon Sadedin, PhD (simon.sadedin{at}vcgs.org.au),
- Mark R. Davis, PhD (mark.davis{at}health.wa.gov.au),
- Fathimath Faiz, PhD (fathimath.faiz{at}health.wa.gov.au),
- Rebecca Gooding, PhD (rebecca.gooding{at}health.wa.gov.au),
- Sarah A. Sandaradura, MBChB, FRACP, PhD (sarah.sandaradura{at}health.nsw.gov.au),
- Gina L. O'Grady, MBChB, FRACP, PhD (ginao{at}adhb.govt.nz),
- Michel C. Tchan, MBBS, FRACP, PhD (michel.tchan{at}health.nsw.gov.au),
- David R. Mowat, MBBS, FRACP (david.mowat{at}health.nsw.gov.au),
- Emily C. Oates, MBBS, FRACP, PhD (e.oates{at}unsw.edu.au),
- Michelle A. Farrar, MBBS, FRACP, PhD (michelle.farrar{at}health.nsw.gov.au),
- Hugo Sampaio, MBBCh, FRACP, MPhil (hugo.sampaio{at}health.nsw.gov.au),
- Alan Ma, MBBS, FRACP (alan.ma{at}health.nsw.gov.au),
- Katherine Neas, MBChB, FRACP (katherine.neas{at}ccdhb.org.nz),
- Min-Xia Wang, PhD (minxia.wang{at}sydney.edu.au),
- Amanda Charlton, MBChB, FRCPA (acharlton{at}adhb.govt.nz),
- Charles Chan, MBBS (Hons), FRCPA, PhD (charles.chan2{at}health.nsw.gov.au),
- Diane N. Kenwright, MBBS, FRCPA (diane.kenwright{at}otago.ac.nz),
- Nicole Graf, MBBS, FRCPA (nicole.graf{at}health.nsw.gov.au),
- Susan Arbuckle, MBBS, FRCPA (susan.arbuckle{at}health.nsw.gov.au),
- Nigel F. Clarke, MBChB, FRACP, PhD* (nnnjournal{at}neurology.org),
- Daniel G. MacArthur, PhD (dgmacarthur{at}gmail.com),
- Kristi J. Jones, MBBS, FRACP, PhD (kristi.jones{at}health.nsw.gov.au),
- Monkol Lek, PhD (monkol.lek{at}yale.edu) and
- Sandra T. Cooper, PhD
- Leigh B. Waddell, PhD (leigh.waddell{at}health.nsw.gov.au),
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(1) World Muscle Society, Travel Fellowship (2)Postgraduate Research Support Scheme (PRSS), grant for conference travel (3)Human Genetics Society of Australasia (HGSA), International Travel Grant
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(1) Kids Neuroscience Centre, Health Manager, 15 years
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National Health and Medical Research Council (NHMRC), PhD scholarship 505004.(Completed in 2011)
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- Samantha J. Bryen, BSc (Hons) (samantha.bryen{at}health.nsw.gov.au),
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- Beryl B. Cummings, PhD (berylc{at}broadinstitute.org),
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Currently employee of Maze Therapeutics, since August 2019. The work done in this manuscript did not overlap my employment in industry.
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- Adam Bournazos, BSc (Hons) (adam.bournazos{at}health.nsw.gov.au),
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- Frances J. Evesson, PhD (frances.evesson{at}health.nsw.gov.au),
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NHMRC Ideas Grant, APP1186084, Chief Investigator B, 2020-2022
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Muscular Dystrophy Association USA, Development Grant 2018-2021
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- Himanshu Joshi, B Software Engineering, B Business (Finance) (himanshu.joshi{at}sydney.edu.au),
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- Jamie L. Marshall, PhD (jmarshal{at}broadinstitute.org),
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1) HyPR-seq: technology for detecting targeted RNA expression at the single cell level.
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1) CZI, 2019-02447, senior group leader, 2019-2021 2) NIH KPMP, U2CDK114886, co-investigator, 2020-2021
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- Taru Tukiainen, PhD (taru.tukiainen{at}gmail.com),
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1. Frontiers in Genetics Genomic Medicine, co-specialty chief editor, 2019-2020
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Academy of Finland, 315589 & 320129, PI, 2018-2023
University of Helsinki
Sigrid Juselius Foundation
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- Elise Valkanas, BA (Biology) (valkanas{at}broadinstitute.org),
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NINDS, F31 NS113414, Principal Investigator, 2019-2022
Harvard Medical School
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- Ben Weisburd, BS (Computer Sc) (weisburd{at}broadinstitute.org),
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- Simon Sadedin, PhD (simon.sadedin{at}vcgs.org.au),
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Victorian Clinical Genetics Services, Head of Clinical Bioinformatics
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- Mark R. Davis, PhD (mark.davis{at}health.wa.gov.au),
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- Fathimath Faiz, PhD (fathimath.faiz{at}health.wa.gov.au),
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- Rebecca Gooding, PhD (rebecca.gooding{at}health.wa.gov.au),
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- Sarah A. Sandaradura, MBChB, FRACP, PhD (sarah.sandaradura{at}health.nsw.gov.au),
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- Gina L. O'Grady, MBChB, FRACP, PhD (ginao{at}adhb.govt.nz),
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Starship Foundation Research Trust - A+7340. New Zealand
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- Michel C. Tchan, MBBS, FRACP, PhD (michel.tchan{at}health.nsw.gov.au),
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Investigator on 3 commercially sponsored trials. None related to the topic of this study.
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Recipient of research funding from NSW PKU Association.
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- David R. Mowat, MBBS, FRACP (david.mowat{at}health.nsw.gov.au),
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- Emily C. Oates, MBBS, FRACP, PhD (e.oates{at}unsw.edu.au),
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Yes - supported by a federal government NHMRC (National Health and Medical Research Council) Early Career Fellowship (GNT1090428) from May 2015.
Supported by a University of New South Wales Academic Salary from Nov 2017.
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- Michelle A. Farrar, MBBS, FRACP, PhD (michelle.farrar{at}health.nsw.gov.au),
Biogen, Roche and Novartis Spinal Muscular Atrophy Therapeutics Scientific Advisory Boards
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Biogen, Roche speaker honoraria
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1. Motor Neuron Diseases Research Institute of Australia Beryl Bayley Postdoctoral Fellowship 2. Motor Neuron Diseases Research Institute of Australia Grant in Aid
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- Hugo Sampaio, MBBCh, FRACP, MPhil (hugo.sampaio{at}health.nsw.gov.au),
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- Alan Ma, MBBS, FRACP (alan.ma{at}health.nsw.gov.au),
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- Katherine Neas, MBChB, FRACP (katherine.neas{at}ccdhb.org.nz),
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- Min-Xia Wang, PhD (minxia.wang{at}sydney.edu.au),
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- Amanda Charlton, MBChB, FRCPA (acharlton{at}adhb.govt.nz),
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- Charles Chan, MBBS (Hons), FRCPA, PhD (charles.chan2{at}health.nsw.gov.au),
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- Diane N. Kenwright, MBBS, FRCPA (diane.kenwright{at}otago.ac.nz),
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- Nicole Graf, MBBS, FRCPA (nicole.graf{at}health.nsw.gov.au),
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- Susan Arbuckle, MBBS, FRCPA (susan.arbuckle{at}health.nsw.gov.au),
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- Nigel F. Clarke, MBChB, FRACP, PhD* (nnnjournal{at}neurology.org),
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- Daniel G. MacArthur, PhD (dgmacarthur{at}gmail.com),
GSK Human Genetics Advisory Board
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Goldfinch Bio, Founder, 2016-
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Biogen, Sanofi-Genzyme, Pfizer, AbbVie
(1) NHGRI/NEI/NHLBI, 1UM1HG008900, MPI, 2016-2019, (2) NHGRI, 1R01HG009141, MPI, 2017-2019, (3) NIDDK, 1U54DK105566, MPI, 2014-2019, (4) NEI, 1R01EY027421, MPI, 2017-2019
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- Kristi J. Jones, MBBS, FRACP, PhD (kristi.jones{at}health.nsw.gov.au),
Biogen SMA Australian Scientific Advisory Boards Sydney, 2015- 2018 Wave Life Sciences - Scientific Advisory Board Sydney 2018 PTC/Link Healthcare Advisory Board, Sydney 2018
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- Monkol Lek, PhD (monkol.lek{at}yale.edu) and
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- Sandra T. Cooper, PhD
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1) Australian Provisional Patent No. 2018904348. Methods of Identifying Genetic Variants. ST Cooper 80% and H Joshi 20% inventive contributions. International PCT filed November 2019. Invention relates to biomarkers underpinning development of a novel splicing prediction algorithm. 2) Australian Provisional Patent No. 2019900836. Intragenic assessment and methods therefor. ST Cooper 100% inventive contributions. International PCT filed March 2020. Invention relates to identification of a novel class of pathogenic splicing variant and our definition of the biophysical parameters required for spliceosome assembly.
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Prof Sandra Cooper is Co-Director of Frontier Genomics Pty Ltd with intent to create a commercial software product that leverages invented IP. Frontier Genomics Pty Ltd has not yet traded and has no investors. Prof CooperÂs time commitment to Frontier Genomics Pty Ltd is provided outside of her USYD role and is not compensated.
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1. AUD$584,314. National Health and Medical Research Council Ideas Grant APP1186084 (2020-22). A new class of genetic splicing variant underlying inherited disorders and cancer. CIA Cooper, CIB Evesson, CIC Joshi. 2. AUD$165,000. Sydney Health Partners NHMRC MRFF Rapid Translation Grant (2019). PI Cooper. Translating technical innovations for splicing diagnostics into clinical genomics. 3. AUD$1.25 million. National Health and Medical Research Council. Project Grant APP1143901 (2018-2022). CIA Cooper, CIB Tam, CIC Graham. PYROXD1 - A novel myopathy disease gene identifies a redox pathway essential for life. 4. AUD $647,000. National Health and Medical Research Council. Senior Research Fellowship APP1116974 (2018-2022). CIA Cooper. Translating genomics to diagnostics and disease mechanism to treatment for patients with inherited neuromuscular disorders.
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My husband holds shares in several Biotechnology companies; Viralytics Avexa Cyclopharm Bioprospect Anteo Diagnostics Stock/Stock Options, Medical Equipment & Materials: My husband holds shares in several Biotechnology companies; Viralytics Avexa Cyclopharm Bioprospect Anteo Diagnostics
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- From the Kids Neuroscience Centre (L.B.W., S.J.B., A.B., F.J.E., H.J., S.A.S., G.L.O., E.C.O., N.F.C., K.J.J., S.T.C.), Kids Research Institute, The Children's Hospital at Westmead, New South Wales, Australia; Discipline of Child and Adolescent Health (L.B.W., S.J.B., A.B., F.J.E., S.A.S., G.L.O., E.C.O., N.F.C., K.J.J., S.T.C.), Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales, Australia; Analytic and Translational Genetics Unit (B.B.C., J.L.M., T.T., E.V., D.G.M., M.L.), Massachusetts General Hospital, Boston; Medical and Population Genetics (B.B.C., J.L.M., T.T., E.V., B.W., S.S., D.G.M., M.L.), and Center for Mendelian Genomics (B.B.C., J.L.M., E.V., B.W., S.S., D.G.M., M.L.), Broad Institute of MIT & Harvard, Cambridge, MA; Functional Neuromics (F.J.E., S.T.C.), Children's Medical Research Institute, Westmead, New South Wales, Australia; Murdoch Children's Research Institute (S.S.), Parkville, Victoria, Australia; Department of Diagnostic Genomics (M.R.D., F.F., R.G.), PathWest Laboratory Medicine WA, Nedlands, Australia; Department of Clinical Genetics (S.A.S., A.M., K.J.J.), Children's Hospital at Westmead, New South Wales, Australia; Department of Genetic Medicine (M.C.T.), Westmead Hospital, New South Wales, Australia; Discipline of Genomic Medicine (M.C.T., A.M.), Sydney Medical School, The University of Sydney, New South Wales, Australia; Centre for Clinical Genetics (D.R.M.), Sydney Children's Hospital, Randwick, New South Wales, Australia; School of Women's and Children's Health (D.R.M., M.A.F.), UNSW Medicine, UNSW Sydney, Australia; Department of Neurology (M.A.F., H.S.), Sydney Children's Hospital, Randwick, New South Wales, Australia; Department of Clinical Genetics (A.M.), Nepean Hospital, Sydney, Australia; Genetic Health Service NZ (K.N.), Wellington, New Zealand; Neurology Laboratory (M.-X.W.), Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; Central Clinical School (M.-X.W.), Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia; Anatomic Pathology (A.C., C.C., N.G., S.A.), The Children's Hospital at Westmead, New South Wales, Australia; Anatomic Pathologist (D.N.K.), Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand; and Harvard Medical School (D.G.M.), Boston, MA.
- Correspondence
Dr. Cooper Sandra.cooper{at}sydney.edu.au
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