NA12932

NA12932 DNA from Fibroblast

Description:

GLYCOGEN STORAGE DISEASE II
GLUCOSIDASE, ALPHA, ACID; GAA

Affected:

Yes

Sex:

Female

Age:

9 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Carbohydrate Metabolism

Quantity

10 µg

Quantitation Method

Please see our FAQ

Cell Type

Fibroblast

Transformant

Untransformed

Sample Source

DNA from Fibroblast

Race

Black/African American

Family Member

Relation to Proband

proband

Confirmation

Biochemical characterization - other

Species

Homo sapiens

Common Name

Human

Remarks

Cardiomegaly; muscle biopsy showed vacuolar myopathy with glycogen storage and deficient acid maltase activity; EM ultrastructure studies consistent with diagnosis; parents are GM12930 (mother) and GM12931 (father); expired at age 9 months; donor subject is a compound heterozygote: allele one has missense mutation caused by a T>C transition at nucleotide 1441 (1441T>C) in exon 10 of the GAA gene which results in a substitution of arginine for tryptophan at codon 481 [Trp481Arg (W481R)]; allele two 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 GM03329 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

Passage Frozen

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

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 1

W481R; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

TRP481ARG

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

Xia Y, Katz M, Chandramohan D, Bechor E, Podgursky B, Hoxie M, Zhang Q, Chertman W, Kang J, Blue E, Chen J, Schleede J, Slotnick NR, Du X, Boostanfar R, Urcia E, Behr B, Cohen J, Siddiqui N, The first clinical validation of whole-genome screening on standard trophectoderm biopsies of preimplantation embryos F&S reports5:63-71 2023

PubMed ID: 38524212

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

Pauly DF, Johns DC, Matelis LA, Lawrence JH, Byrne BJ, Kessler PD, Complete correction of acid alpha-glucosidase deficiency in Pompe disease fibroblasts in vitro, and lysosomally targeted expression in neonatal rat cardiac and skeletal muscle. Gene Ther5(4):473-80 1998

PubMed ID: 9614571