GM03329

GM03329 Fibroblast

Description:

GLYCOGEN STORAGE DISEASE II
GLUCOSIDASE, ALPHA, ACID; GAA

Affected:

Yes

Sex:

Male

Age:

2 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Carbohydrate Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

Black/African American

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Infantile onset; normal size (3.6 kb) and amount of mRNA for GAA, GAA protein detected by antibody, but deficient acid-alpha-1,4 glucosidase (0.35%); hypotonia; donor subject is a compound heterozygote with only one allele expressed: allele one carries a A>G transition at nucleotide 1555 (1555A>G) in exon 11 which results in a substitution of valine for methionine at codon 519 [Met519Val (M519V)]; allele two (the silent allele) contains a G>A transition at the first nucleotide of intron 8 (IVS8+1G>A) of the GAA gene which results in a splicing defect at the 5’ donor site; this rare allele was also found in GM12932 and 18 polymorphisms in the GAA gene were identical in both lines suggesting common ancestry (Raben et al. Hum. Mutat. 13:83-84 (1999)].

Characterizations

PDL at Freeze

2.69

Passage Frozen

alpha-glucosidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.20; 0.35% activity.

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 1

M519V; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

MET519VAL

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 2

; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

IVS8+1G>A

Phenotypic Data

Remarks

Publications

Raben N, Lee E, Lee L, Hirschhorn R, Plotz PH, Novel mutations in African American patients with glycogen storage disease Type II. Mutations in brief no. 209. Online. Hum Mutat13(1):83-4 1999

PubMed ID: 10189220

Becker JA, Vlach J, Raben N, Nagaraju K, Adams EM, Hermans MM, Reuser AJ, Brooks SS, Tifft CJ, Hirschhorn R, Huie ML, Nicolino M, Plotz PH, The African origin of the common mutation in African American patients with glycogen-storage disease type II. Am J Hum Genet62(4):991-4 1998

PubMed ID: 9529346

Huie ML, Hirschhorn R, Chen AS, Martiniuk F, Zhong N, Mutation at the catalytic site (M519V) in glycogen storage disease type II (Pompe disease). Hum Mutat4(4):291-3 1994

PubMed ID: 7866409

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, Bodkin M, Tzall S, Hirschhorn R, Identification of the base-pair substitution responsible for a human acid alpha glucosidase allele with lower "affinity" for glycogen (GAA 2) and transient gene expression in deficient cells. Am J Hum Genet47(3):440-5 1990

PubMed ID: 2203258

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