GM00244

GM00244 Fibroblast

Description:

GLYCOGEN STORAGE DISEASE II
GLUCOSIDASE, ALPHA, ACID; GAA

Affected:

Yes

Sex:

Female

Age:

5 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Carbohydrate Metabolism

Alternate IDs

GM17061 [GLYCOGEN STORAGE DISEASE II]

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Ethnicity

MEXICAN

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Infantile onset; Mexican; normal size and amount of mRNA for GAA, GAA protein detected by antibody, but deficient acid alpha-1,4 glucosidase activity (0.16%); 46,XX; donor subject is a compound heterozygote: allele one carries a C>T transition at nucleotide 2560 in exon 18 of the GAA gene (2560C>T) which results in a nonsense codon at amino acid 854 [Arg854Ter (R854X)]; allele two carries a missense mutation caused by a T>C transition at nucleotide 953 (953T>C) in exon 5 which results in the substitution of threonine for methionine at codon 318 [Met318Thr (M318T)]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

alpha-glucosidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.20; 0.16% activity.

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 1

606800.0015; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

ARG854TER; Becker et al. [Am. J. Hum. Genet. 62: 991-994 (1998)] found a high frequency of the arg854-to-ter mutation of the GAA gene in compound heterozygous or homozygous state in cases of glycogen storage disease II (232300) in various African populations and in African-American patients.

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 2

606800.0002; GLYCOGEN STORAGE DISEASE TYPE II, INFANTILE FORM

Identified Mutation

MET318THR; In a case of infantile-onset glycogen storage disease type II (cell line GM00244), Zhong et al. [Am J Hum Genet 49:635 (1991)] found a T-to-C transition at nucleotide 953 of the GAA gene, which predicted a methionine-to-threonine subsitution at residue 318 of the enzyme. This missense mutation was not detected in 37 additional GAA-deficient chromosomes. The patient was a genetic compound with the second allele expressing almost no mRNA.

Phenotypic Data

Remarks

Publications

Prince WS, McCormick LM, Wendt DJ, Fitzpatrick PA, Schwartz KL, Aguilera AI, Koppaka V, Christianson TM, Vellard MC, Pavloff N, Lemontt JF, Qin M, Starr CM, Bu G, Zankel TC, Lipoprotein receptor binding, cellular uptake and lysosomal delivery of fusions between the receptor-associated protein (RAP) and alpha-L-iduronidase or acid alpha-glucosidase. J Biol ChemEpub ahead of print: 2004

PubMed ID: 15170390

Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA, Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol41(1):90-6 2003

PubMed ID: 12517831

Zhong N, Martiniuk F, Tzall S, Hirschhorn R, Identification of a missense mutation in one allele of a patient with Pompe disease, and use of endonuclease digestion of PCR-amplified RNA to demonstrate lack of mRNA expression from the second allele. Am J Hum Genet49:635-45 1991

PubMed ID: 1652892

Martiniuk F, Mehler M, Tzall S, Meredith G, Hirschhorn R, Extensive genetic heterogeneity in patients with acid alpha glucosidase deficiency as detected by abnormalities of DNA and mRNA. Am J Hum Genet47:73-8 1990

PubMed ID: 2112341

Beratis NG, LaBadie GU, Hirschhorn K, Genetic heterogeneity in acid alpha-glucosidase deficiency. Am J Hum Genet35:21-33 1983

PubMed ID: 6401921

Brown DH, Brown BI, Studies of the residual glycogen branching enzyme activity present in human skin fibroblasts from patients with type IV glycogen storage disease. Biochem Biophys Res Commun111:636-43 1983

PubMed ID: 6220706

Hasilik A, Neufeld EF, Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. J Biol Chem255:4946-50 1980

PubMed ID: 6989822