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
- Univ. of Colorado School of Medicine, Denver, CO (United States); and others
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 academia 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. 13 refs., 5 figs., 3 tabs.
- OSTI ID:
- 508217
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 59; ISSN 0002-9297; ISSN AJHGAG
- Country of Publication:
- United States
- Language:
- English
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BASIC STUDIES
AMINO ACIDS
DIAPHORASE
DNA SEQUENCING
DNA-CLONING
ELECTROPHORESIS
ENZYME ACTIVITY
ESCHERICHIA COLI
GENE MUTATIONS
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 19
METABOLIC DISEASES
METABOLISM
NERVOUS SYSTEM DISEASES
PATIENTS
PENNSYLVANIA
POLYMERASE CHAIN REACTION
RECESSIVE MUTATIONS
STRUCTURE-ACTIVITY RELATIONSHIPS