NA11661

NA11661 DNA from Fibroblast

Description:

GLYCOGEN STORAGE DISEASE II
GLUCOSIDASE, ALPHA, ACID; GAA

Affected:

Yes

Sex:

Male

Age:

38 YR (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

White

Ethnicity

ITALIAN

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Abnormal liver function tests; occasional charley-horse in legs during physical activity; morning headaches; intolerance to greasy foods; abdominal cyst; deficient fibroblast and WBC acid-alpha-1,4 glucosidase activity; 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 carries a deletion of exon 18

Characterizations

PDL at Freeze

3.58

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

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

606800.0012; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

EX18DEL; Van der Kraan et al. [Biochem. Biophys. Res. Commun. 203: 1535-1541 (1994)] reported that deletion of exon 18 of the GAA gene is a frequent mutation in Pompe disease (232300). Huie et al. [Hum. Molec. Genet. 3: 2231-2236 (1994)] found this mutation in patients with both infantile and adult forms of this disease. Vorgerd et al. [Neurogenetics 1: 205-211 (1998)] found homozygosity for the exon 18 deletion in 2 affected sibs and an unrelated patient with adult type GSD II.

Phenotypic Data

Remarks

Publications

La Cognata V, Cavallaro S, Detection of Structural Variants by NGS: Revealing Missing Alleles in Lysosomal Storage Diseases Biomedicines10: 2022

PubMed ID: 36009380

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