GM06314

GM06314 LCL from B-Lymphocyte

Description:

GLYCOGEN STORAGE DISEASE II
GLUCOSIDASE, ALPHA, ACID; GAA

Affected:

Yes

Sex:

Female

Age:

40 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Carbohydrate Metabolism

Alternate IDs

GM17323 [GLYCOGEN STORAGE DISEASE II]

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

ITALIAN

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Adult onset; respiratory arrest; muscle weakness onset at age 35; GAA mRNA showed two bands: one normal size band (3.6 kb) of half-normal amount and one band of reduced amount and size (approximately 3 kb); alpha-1,4 glucosidase deficiency: 1-2% of normal activity in lymphoblasts; similarly affected sister; donor subject is a compound heterozygote: allele one carries a T>G transversion at position -13 of the acceptor site of intron 1 of the GAA gene (IVS1-13T>G); the resulting alternatively spliced transcript has an in frame deletion of exon 2 which contains the initiation codon; allele two which contains a rare mutation has a G>C transversion at position +1 in intron 10 (IVS10+1G>C) which results in the splicing out of exon 10 including part of the enzyme catalytic site

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227.

alpha-glucosidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.20; 1-2% 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.

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 2

; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

IVS10+1G>C

Phenotypic Data

Remarks

Publications

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