Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene.
Medium chain acyl-CoA dehydrogenase (MCAD) catalyzes the first reaction of the beta-oxidation cycle for 4-10-carbon fatty acids. MCAD deficiency is one of the most frequent inborn metabolic disorders in populations of northwestern European origin. In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified. Among them, a single prevalent mutation, 985A-->G, was found in 90% of 344 variant alleles. 985A-->G causes glutamate substitution for lysine-304 in the mature MCAD subunit, which causes impairment of tetramer assembly and instability of the protein. Three of 7 rarer mutations have been identified in a few unrelated patients, while the remaining 4 have each been found in only a single pedigree. In addition to tabulating the mutations, the acyl-CoA dehydrogenase gene family, the structure of the MCAD gene and the evolution of 985A-->G mutation are briefly discussed.
Tanaka
K
K
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510.
Yokota
I
I
Coates
P M
PM
Strauss
A W
AW
Kelly
D P
DP
Zhang
Z
Z
Gregersen
N
N
Andresen
B S
BS
Matsubara
Y
Y
Curtis
D
D
D042964:Acyl-CoA Dehydrogenase; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length
D004247:DNA; D044944:Acyl-CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase