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Title: 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

Abstract

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.

Authors:
; ;  [1]
  1. Univ. of Colorado School of Medicine, Denver, CO (United States) [and others
Publication Date:
OSTI Identifier:
508217
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 59; Journal Issue: 5; Other Information: PBD: Nov 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; METABOLIC DISEASES; HEREDITARY DISEASES; NERVOUS SYSTEM DISEASES; AMINO ACIDS; METABOLISM; DIAPHORASE; STRUCTURE-ACTIVITY RELATIONSHIPS; GENE MUTATIONS; ENZYME ACTIVITY; DNA-CLONING; DNA SEQUENCING; GENETIC MAPPING; HUMAN CHROMOSOME 19; POLYMERASE CHAIN REACTION; ELECTROPHORESIS; RECESSIVE MUTATIONS; PENNSYLVANIA; ESCHERICHIA COLI

Citation Formats

Biery, B.J., Stein, D.E., and Goodman, S.I.. 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. United States: N. p., 1996. Web.
Biery, B.J., Stein, D.E., & Goodman, S.I.. 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. United States.
Biery, B.J., Stein, D.E., and Goodman, S.I.. Fri . "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". United States.
@article{osti_508217,
title = {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},
author = {Biery, B.J. and Stein, D.E. and Goodman, S.I.},
abstractNote = {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.},
doi = {},
journal = {American Journal of Human Genetics},
number = 5,
volume = 59,
place = {United States},
year = {Fri Nov 01 00:00:00 EST 1996},
month = {Fri Nov 01 00:00:00 EST 1996}
}