Molecular and structural analysis of two novel mutations in a patient withMut(-) methylmalanyl-CoA deficiency

Inherited defects in the gene encoding the methylnalonyl-CoA mutase (MCM) r esult in the mut forms of methylmalonic aciduria (MMA). Twelve mutations ha ve been identified associated with the mut(-) phenotype. We report two nove l mutations (R621N and D156N) in a compound heterozygote mut- patient. Thes e two mutations and three previously published ones (H627N, A191E, Y231N) w ere mapped onto a three dimensional homology model of the human MCM constru cted from the crystal structure of the Propionibacterium shermanii enzyme. (C) 2001 Academic Press.