Identification of eight novel mutations of the acid α-glucosidase gene causing the infantile or juvenile form of glycogen storage disease type II
Journal
Journal of Neurology
Journal Volume
255
Journal Issue
6
Pages
831-838
ISSN
1432-1459
Date Issued
2008-06
Author(s)
Abstract
Glycogen-storage disease type II (GSDII; OMIM #232300), an autosomal recessive disorder caused by a deficiency of the glycogen hydrolysis enzyme acid α-glucosidase (acid GAA; acid maltase, EC. 3.2.10.20), results in the accumulation of glycogen in the lysosome. We performed a molecular genetic study on 29 patients with infantile-onset glycogen-storage disease type II (GSDII), 6 with juvenile-onset GSDII and one carrier for GSDII. Seventeen different mutations were identified among them; 8 were novel mutations: c.421C > A (p.L141M), c.872T > C (p.L291P), c.893A > C (p.Y298S), c.1375G > A (p.D459N), c.1437G > C (p.K479N), c.1509_1511del (p.A504del), c.1960T > C (p.S654P), and c.2174G > C (p.R725P). One of the mutations identified, c.2238G > C (p.W746C), which was a sequence change of unknown pathogenic significance causing diminished enzyme activity, was found homozygously in a juvenile-onset patient. We also found a juvenile-onset patient with homozygote c.1935C > A mutation which was frequently found in infantile-onset patients. In addition to mutations, we also identified 14 new polymorphisms in the acid α-glucosidase gene. The genotype/phenotype correlations indicated that c.2238G > C (p.W746C) is correlated with juvenile- onset GSDII and that c.872T > C (p.L291P) and c.1411_1414del (p.E471fsX5) are correlated with infantile-onset GSDII. Mutational analysis of GAA is useful in genetic counseling and prenatal diagnosis of the disease. ? 2008 Springer.
Subjects
Acid α-glucosidase; Glycogen storage disease type II; Mutation analysis; Novel mutation; Pompe disease
SDGs
Other Subjects
alpha glucosidase; adolescent; adult; article; childhood disease; clinical article; controlled study; disease carrier; enzyme activity; gene identification; gene mutation; genetic analysis; genetic counseling; genotype phenotype correlation; glycogen storage disease type 2; human; infant disease; onset age; prenatal diagnosis; priority journal; school child; single nucleotide polymorphism; Adult; alpha-Glucosidases; Asian Continental Ancestry Group; DNA Mutational Analysis; Gene Expression Regulation, Enzymologic; Genetic Markers; Genetic Predisposition to Disease; Genetic Screening; Genotype; Glycogen Storage Disease Type II; Homozygote; Humans; Middle Aged; Mutation; Phenotype; Polymorphism, Genetic; Taiwan
Type
journal article