Identification of Eight Novel Mutations of the Acid Alpha-Glucosidase Gene Causing the Infantile or Juvenile Form of Glycogen Storage Disease Type Ii
Resource
JOURNAL OF NEUROLOGY v.255 n.6 pp.831-838
Journal
JOURNAL OF NEUROLOGY
Journal Volume
v.255
Journal Issue
n.6
Pages
831-838
Date Issued
2008
Date
2008
Author(s)
WAN, LEI
LEE, CHENG-CHUN
HSU, CHIN-MOO
HWU, WUH-LIANG
YANG, CHIH-CHAO
TSAI, CHANG-HAI
TSAI, FUU-JEN
Abstract
Glycogen-storage disease type II (GSDII; OMIM #232300), an autosomal recessive disorder caused by a deficiency of the glycogen hydrolysis enzyme acid alpha-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 alpha- 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.
Subjects
glycogen storage disease type II
Pompe disease
acid alpha- glucosidase
novel mutation
mutation analysis
Type
journal article