title: Atypical methylmalonic aciduria: frequency of mutations in the methylmalonyl CoA epimerase gene (MCEE).
abstract: Methylmalonic aciduria is known to result from defects in the enzyme methylmalonyl CoA mutase (MCM) (mut complementation group) and from defects in the synthesis of the MCM cofactor adenosylcobalamin (cblA, cblB, cblC, cblD, and cblF groups). Two patients who excrete methylmalonic acid have recently been shown to have a homozygous nonsense mutation in the gene coding for methylmalonyl CoA epimerase (MCEE). To further understand the cause of methylmalonic acid excretion, the MCEE gene was sequenced in 229 patients with elevations of methylmalonic acid excretion for which no cause was known. Mutations in MCEE were detected in five patients: two patients homozygous for c.139C>T, p.R47X, one patient homozygous for c.178A>C, p.K60Q, and two patients heterozygous for c.427C>T, p.R143C. Fusion of fibroblast lines from two patients homozygous for c.139C>T, p.R47X did not result in correction of [(14)C]propionate incorporation toward control values while the defect in these fibroblasts was complemented by mut, cblA, and cblB fibroblasts. Infection with wild-type MCEE cDNA resulted in correction of the biochemical phenotype in cells from both patients.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: Abigail B
authors.initials: AB
authors.lastname: Gradinger
authors.forename: Caroline
authors.initials: C
authors.lastname: Bélair
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Worgan
authors.forename: Carter D
authors.initials: CD
authors.lastname: Li
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Lavallée
authors.forename: David
authors.initials: D
authors.lastname: Roquis
authors.forename: David
authors.initials: D
authors.lastname: Watkins
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenblatt
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D002460:Cell Line; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008764:Methylmalonic Acid / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D019998:Racemases and Epimerases / Q000235:genetics*