title: Seven novel mutations in mut methylmalonic aciduria.
abstract: Methylmalonic aciduria (MMA) is an autosomal recessive inborn error of metabolism that results from functional defects in methylmalonyl CoA mutase (MCM), a nuclear-encoded, mitochondrial enzyme that uses the vitamin B12 derivative, adenosylcobalamin (AdoCbl) as a cofactor. To date, 23 mutations have been identified at the MUT locus on the short arm of chromosome 6, causing the mut forms of MMA (mut complementation group; mut MMA, McKusick #251000). We now report seven novel mutations. Three were found inmut0 patients: R228Q (c759G-->A) was found as a heterozygous change; G312V (c1011G-->T) and 346delL (c1112delCTT) were both found as homozygous changes. Four mutations were found in mut patients: A191E (c648C-->A) and V633G (c1974T-->G) were found in the same patient; 684insL (c2128insCTC) and L685R (c2130T-->G) were both found as homozygous changes. The recent modelling of the human methylmalonyl CoA mutase allowed for an interpretation of the identified mutations.
authors.affiliation: Medical Research Council of Canada Genetics Group and Department of Human Genetics, McGill University, Montreal, Quebec.
authors.forename: C E
authors.initials: CE
authors.lastname: Adjalla
authors.forename: A R
authors.initials: AR
authors.lastname: Hosack
authors.forename: B M
authors.initials: BM
authors.lastname: Gilfix
authors.forename: E
authors.initials: E
authors.lastname: Lamothe
authors.forename: S
authors.initials: S
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Chan
authors.forename: S
authors.initials: S
authors.lastname: Evans
authors.forename: N V
authors.initials: NV
authors.lastname: Matiaszuk
authors.forename: D S
authors.initials: DS
authors.lastname: Rosenblatt
mesh_terms: D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics* / Q000652:urine; D001483:Base Sequence; D002460:Cell Line; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005816:Genetic Complementation Test; D006801:Humans; D008764:Methylmalonic Acid / Q000652:urine*; D008765:Methylmalonyl-CoA Mutase / Q000172:deficiency / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D008764:Methylmalonic Acid; D004247:DNA; D008765:Methylmalonyl-CoA Mutase