학술논문
Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants in GPAA1
Document Type
Academic Journal
Author
Castle, Alison M.R.; Salian, Smrithi; Bassan, Haim; Sofrin-Drucker, Efrat; Cusmai, Raffaella; Herman, Kristin C.; Heron, Delphine; Keren, Boris; Johnstone, Devon L.; Mears, Wendy; Morlot, Susanne; Nguyen, Thi Tuyet Mai; Rock, Rachel; Stolerman, Elliot; Russo, Julia; Burns, William Boyce; Jones, Julie R.; Serpieri, Valentina; Wallaschek, Hannah; Zanni, Ginevra; Dyment, David A.; Campeau, Philippe M.
Source
Neurology: Genetics. Dec 01, 2021 7(6):e631-e631
Subject
Language
English
ISSN
2376-7839
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.