7 NOVEL MUTATIONS IN MUT METHYLMALONIC ACIDURIA

Methylmalonic aciduria (MNA) 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 vi tamin B-12 derivative, adenosylcobalamin (AdoCbl) as a cofactor. To da te, 23 mutations have been identified at the MUT locus on the short ar m of chromosome 6, causing the mut forms of MMA (mut complementation g roup; mut MMA, McKusick #251000). We now report seven novel mutations. Three were found in mut(0) patients: R228Q (c759G-->A) was found as a heterozygous change; G312V (c1011G-->T) and 346delL (c1112delCTT) wer e 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 (c2130T0-->G) were both found as homozygous changes. The recent modelling of the human methyl malonyl CoA mutase allowed for an interpretation of the Identified mut ations. (C) 1998 Wiley-Liss, Inc.