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Arginine 302 mutations in the pyruvate dehydrogenase E1α subunit gene: Identification of further patients and in vitro demonstration of pathogenicity
Author(s) -
Otero Lucy J.,
Brown Ruth M.,
Brown Garry K.
Publication year - 1998
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1998)12:2<114::aid-humu6>3.0.co;2-#
Subject(s) - biology , pyruvate dehydrogenase complex , mutation , mutant , arginine , protein subunit , gene , microbiology and biotechnology , pyruvate dehydrogenase phosphatase , pyruvate dehydrogenase lipoamide kinase isozyme 1 , genetics , enzyme , amino acid , biochemistry
Three further patients with mutations in the codon for arginine 302 of the E1α subunit of the pyruvate dehydrogenase complex have been identified. Mutations in this codon have now been found in nine patients with pyruvate dehydrogenase deficiency in seven unrelated families, in sharp contrast to the great majority of other PDH E1α mutations which have been described in single individuals only. Because of the relatively high frequency of this mutation and because very few PDH E1α mutations have been demonstrated to be causative, we have established a system for analysing the consequences of defined mutations using transfection of normal and mutant PDH E1α cDNA into transformed human fibroblasts which have no endogenous E1α mRNA or protein. Using this test system, we have demonstrated that the R302C mutation results in the production of PDH E1α protein which is devoid of enzymic activity. Hum Mutat 12:114–121, 1998. © 1998 Wiley‐Liss, Inc.