Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease.

Journal Article (Journal Article)

Deficiency of glycogen debranching enzyme (AGL) activity causes glycogen storage disease type III (GSD-III). Generalized loss of AGL activity results in GSD-IIIa, and muscle-specific retention of AGL activity results in GSD-IIIb. To date, no common mutation has been described among GSD-III patients, except for three alleles; two linked specifically with GSD-IIIb, and the third found only in North African Jews with GSD-IIIa. Here we report two frequent mutations, each of which was found in the homozygous state in multiple patients, and each of which was associated with a subset of clinical phenotype in those patients with that mutation. A novel point mutation of a single T deletion at cDNA position 3964 (3964delT) was first detected in an African American patient, who has a severe phenotype and early onset of clinical symptoms. The second mutation was an A to G transition at position -12 upstream of the 3' splice site of intron 32 (IVS32-12A > G). This lesion, previously implicated as a IIIb mutation in a Japanese patient, was identified in a confirmed GSD-IIIa Caucasian patient presenting with mild clinical symptoms. These two mutations together account for more than 12% of the molecular defects in the GSD-III patients tested. Our molecular and clinical data suggest a genotype-phenotype correlation for each of these mutations. Furthermore, this current study, coupled with our previous reports, describes the molecular tools necessary for the development of a DNA-based diagnostic test for GSD-III.

Full Text

Duke Authors

Cited Authors

  • Shaiu, WL; Kishnani, PS; Shen, J; Liu, HM; Chen, YT

Published Date

  • January 2000

Published In

Volume / Issue

  • 69 / 1

Start / End Page

  • 16 - 23

PubMed ID

  • 10655153

International Standard Serial Number (ISSN)

  • 1096-7192

Digital Object Identifier (DOI)

  • 10.1006/mgme.1999.2953


  • eng

Conference Location

  • United States