NA00248

NA00248 DNA from Fibroblast

Description:

GLYCOGEN STORAGE DISEASE II
GLUCOSIDASE, ALPHA, ACID; GAA

Affected:

Yes

Sex:

Male

Age:

5 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Carbohydrate Metabolism

Quantity

50 µg

Quantitation Method

Please see our FAQ

Cell Type

Fibroblast

Transformant

Untransformed

Sample Source

DNA from Fibroblast

Race

Black/African American

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Infantile onset; deficient acid-alpha-1,4 glucosidase (0.27%); no detectable levels of GAA mRNA or protein; passage 3 at CCR; donor subject is homozygous for a C>T transition at nucleotide 2560 in exon 18 of the GAA gene (2560C>T) which results in a nonsense codon at amino acid 854 [Arg854Ter (R854X)]; cross-reactive immunological material (CRIM)-negative status confirmed by Western blot and GAA sequencing analyses (homozygous for p.Arg854X)(PMID:24044919).

Characterizations

PDL at Freeze

6.2

Passage Frozen

alpha-glucosidase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.20; 0.27% activity.

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 1

606800.0015; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

ARG854TER; Becker et al. [Am. J. Hum. Genet. 62: 991-994 (1998)] found a high frequency of the arg854-to-ter mutation of the GAA gene in compound heterozygous or homozygous state in cases of glycogen storage disease II (232300) in various African populations and in African-American patients.

Gene

GAA

Chromosomal Location

17q25.2-q25.3

Allelic Variant 2

606800.0015; GLYCOGEN STORAGE DISEASE TYPE II

Identified Mutation

Phenotypic Data

Remarks

Publications

Cheng YS, Li R, Baskfield A, Beers J, Zou J, Liu C, Zheng W, A human induced pluripotent stem cell line (TRNDi007-B) from an infantile onset Pompe patient carrying pR854X mutation in the GAA gene Stem cell research37:101435 2019

PubMed ID: 31026687

Kang JY1, Shin KK1, Kim HH2, Min JK3,4, Ji ES5, Kim JY5, Kwon O6,7, Oh DB, Lysosomal Targeting Enhancement by Conjugation of Glycopeptides Containing Mannose-6-phosphate Glycans Derived from Glyco-engineered Yeast Scientific Reports8:8730 2018

PubMed ID: 29880804

Z. Wang, et al, A new assay for fast, reliable CRIM status determination in infantile-onset Pompe disease. Mol Genet Metab. 2013 Aug 29. pii: S1096-7192(13)00300-4. doi: 10.1016/j.ymgme.2013.08.010. [Epub ahead of print]8:8730 2013

PubMed ID: 24044919

Nishiyama Y, Shimada Y, Yokoi T, Kobayashi H, Higuchi T, Eto Y, Ida H, Ohashi T, Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease Molecular genetics and metabolism107:490-5 2012

PubMed ID: 23041259

Moreland RJ, Higgins S, Zhou A, Vanstraten P, Cauthron RD, Brem M, McLarty BJ, Kudo M, Canfield WM, Species-specific differences in the processing of acid a-glucosidase are due to the amino acid identity at position 201 Gene491:25-30 2011

PubMed ID: 21963446

Moreland RJ, Jin X, Zhang XK, Decker RW, Albee KL, Lee KL, Cauthron RD, Brewer K, Edmunds T, Canfield WM, Lysosomal acid alpha-glucosidase consists of four different peptides processed from a single chain precursor. J Biol Chem280(8):6780-91 2005

PubMed ID: 15520017

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

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

Hasilik A, Neufeld EF, Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. J Biol Chem255:4946-50 1980

PubMed ID: 6989822

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

Pena SD, Wrogemann K, Searching for molecular abnormalities in genetic diseases by the use of a double labeling technique. I. Rationale, techniques, and initial evaluation. Pediatr Res12:887-93 1978

PubMed ID: 714535