Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish

Am J Hum Genet. 1996 Nov;59(5):1006-11.


The structure of the human glutaryl coenzyme A dehydrogenase (GCD) gene was determined to contain 11 exons and to span approximately 7 kb. Fibroblast DNA from 64 unrelated glutaric acidemia type I (GA1) patients was screened for mutations by PCR amplification and analysis of SSCP. Fragments with altered electrophoretic mobility were subcloned and sequenced to detect mutations that caused GA1. This report describes the structure of the GCD gene, as well as point mutations and polymorphisms found in 7 of its 11 exons. Several mutations were found in more than one patient, but no one prevalent mutation was detected in the general population. As expected from pedigree analysis, a single mutant allele causes GA1 in the Old Order Amish of Lancaster County, Pennsylvania. Several mutations have been expressed in Escherichia coli, and all produce diminished enzyme activity. Reduced activity in GCD encoded by the A421V mutation in the Amish may be due to impaired association of enzyme subunits.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / epidemiology
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Cells, Cultured
  • Escherichia coli / genetics
  • Fibroblasts / enzymology
  • Glutarates / metabolism
  • Glutaryl-CoA Dehydrogenase
  • Humans
  • Oxidoreductases / genetics*
  • Oxidoreductases Acting on CH-CH Group Donors*
  • Pennsylvania
  • Point Mutation
  • Polymorphism, Genetic
  • Sequence Analysis, DNA


  • Glutarates
  • Oxidoreductases
  • Oxidoreductases Acting on CH-CH Group Donors
  • Glutaryl-CoA Dehydrogenase

Associated data

  • GENBANK/AF012339
  • GENBANK/AF012340
  • GENBANK/AF012341
  • GENBANK/AF012342