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GAA variants and phenotypes among 1,079 patients with Pompe disease: Data from the Pompe Registry
Author(s) -
Reuser Arnold J. J.,
Ploeg Ans T.,
Chien YinHsiu,
Llerena Juan,
Abbott MaryAlice,
Clemens Paula R.,
Kimonis Virginia E.,
Leslie Nancy,
Maruti Sonia S.,
Sanson BerndJan,
Araujo Roberto,
Periquet Magali,
Toscano Antonio,
Kishnani Priya S.
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23878
Subject(s) - disease , clinical phenotype , biology , age of onset , observational study , phenotype , cardiomyopathy , bioinformatics , medicine , genetics , gene , heart failure
Identification of variants in the acid α‐glucosidase ( GAA ) gene in Pompe disease provides valuable insights and systematic overviews are needed. We report on the number, nature, frequency, and geographic distribution of GAA sequence variants listed in the Pompe Registry, a long‐term, observational program and the largest global repository of Pompe disease data. Variant information was reviewed and compared with publicly available GAA databases/resources. Among 1,079 eligible patients, 2,075 GAA variants (80 unique novel) were reported. Variants were listed by groups representing Pompe disease phenotypes. Patients were classified as Group A: Symptom onset ≤ 12 months of age with cardiomyopathy; Group B: Symptom onset ≤ 12 years of age (includes patients with symptom onset ≤ 12 months of age without cardiomyopathy); or Group C: Symptom onset > 12 years of age. Likely impact of novel variants was predicted using bioinformatics algorithms. Variants were classified by pathogenicity using ACMG guidelines. Data reported from the Pompe Registry provide new information about the distribution of GAA variants globally and across the clinical spectrum, add to the number and diversity of GAA variants registered in public databases through published data sharing, provide a first indication of the severity of novel variants, and assist in diagnostic practice and outcome prediction.