GM00443

GM00443 Fibroblast

Description:

GLYCOGEN STORAGE DISEASE II
GLUCOSIDASE, ALPHA, ACID; GAA

Affected:

Yes

Sex:

Male

Age:

30 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

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Adult form; onset in third decade; normal size and amount of mRNA for GAA, GAA protein detected by antibody, but only 9 to 26% of normal acid-alpha-1,4 glucosidase activity; passage 3 at CCR; donor subject is heterozygous with one allele carrying a T>G transversion at position -13 of the acceptor site of intron 1 of the GAA gene, resulting in alternatively spliced transcripts with deletion of the first coding exon [exon 2 (IVS1-13T>G)]

Characterizations

PDL at Freeze

5.11

alpha-glucosidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.20; 9-26% activity.

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 1

606800.0006; GLYCOGEN STORAGE DISEASE TYPE II, ADULT FORM

Identified Mutation

IVS1AS, T>G, -13; Huie et al. [Hum. Molec. Genet. 3: 2231-2236 (1994)] identified a T-to-G transversion at position -13 of the acceptor site of intron 1 of the GAA gene, resulting in alternatively spliced transcripts with deletion of the first coding exon, exon 2, in patients with the adult onset form of Pompe disease (232300). This mutation was found in 28 of 41 adult onset cases examined. Kroos et al. [J. Med. Genet. 32: 836-837 (1995)] showed this mutation in 38 of 50 heterozygous persons with the adult form of the disease and in 4 of 13 heterozygous patients with juvenile form, but did not find the mutation in children with the infantile form of Pompe disease.

Phenotypic Data

Remarks

Publications

Aung-Htut MT, Ham KA, Tchan M, Johnsen R, Schnell FJ, Fletcher S, Wilton SD, Splice modulating antisense oligonucleotides restore some acid-alpha-glucosidase activity in cells derived from patients with late-onset Pompe disease Scientific reports10:6702 2020

PubMed ID: 32317649

Huie ML, Chen AS, Tsujino S, Shanske S, DiMauro S, Engel AG, Hirschhorn R, Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (-13T-->G) mutation in a majority of patients and a novel IVS10 (+1GT-->CT) mutation. Hum Mol Genet3:2231-6 1994

PubMed ID: 7881425

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

Pena SD, Quilliam NM, Hamerton JL, Wrogemann K, Searching for molecular abnormalities in genetic diseases by the use of a double labeling technique. II. Deficiency of a basic protein in fibroblasts of patients with Pompe's disease. Pediatr Res12:894-8 1978

PubMed ID: 362358