PT  - JOURNAL ARTICLE
AU  - Castle, Alison M.R.
AU  - Salian, Smrithi
AU  - Bassan, Haim
AU  - Sofrin-Drucker, Efrat
AU  - Cusmai, Raffaella
AU  - Herman, Kristin C.
AU  - Heron, Delphine
AU  - Keren, Boris
AU  - Johnstone, Devon L.
AU  - Mears, Wendy
AU  - Morlot, Susanne
AU  - Nguyen, Thi Tuyet Mai
AU  - Rock, Rachel
AU  - Stolerman, Elliot
AU  - Russo, Julia
AU  - Burns, William Boyce
AU  - Jones, Julie R.
AU  - Serpieri, Valentina
AU  - Wallaschek, Hannah
AU  - Zanni, Ginevra
AU  - Dyment, David A.
AU  - Campeau, Philippe M.
TI  - Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants in <em>GPAA1</em>
AID  - 10.1212/NXG.0000000000000631
DP  - 2021 Dec 01
TA  - Neurology Genetics
PG  - e631
VI  - 7
IP  - 6
4099  - http://ng.neurology.org/content/7/6/e631.short
4100  - http://ng.neurology.org/content/7/6/e631.full
SO  - Neurol Genet2021 Dec 01; 7
AB  - 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.AP=anchored protein; ALP=alkaline phosphatase; FLAER=fluorescein-labeled proaerolysin; GPI=glycosylphosphatidylinositol; WES=whole-exome sequencing