title: Identification of eight novel mutations of the acid alpha-glucosidase gene causing the infantile or juvenile form of glycogen storage disease type II.
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.
authors.affiliation: Dept. of Medical Genetics and Medical, Research, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung, Taiwan.
authors.forename: L
authors.initials: L
authors.lastname: Wan
authors.forename: C-C
authors.initials: CC
authors.lastname: Lee
authors.forename: C-M
authors.initials: CM
authors.lastname: Hsu
authors.forename: W-L
authors.initials: WL
authors.lastname: Hwu
authors.forename: C-C
authors.initials: CC
authors.lastname: Yang
authors.forename: C-H
authors.initials: CH
authors.lastname: Tsai
authors.forename: F-J
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006009:Glycogen Storage Disease Type II / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D013624:Taiwan; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C509951:GAA protein, human; D000520:alpha-Glucosidases