mut0 methylmalonic acidemia: eleven novel mutations of the methylmalonyl CoA mutase including a deletion-insertion mutation.
Methylmalonic aciduria (MMA) is an autosomal-recessive disorder caused by inadequate function of methylmalonyl-CoA mutase (MCM), a nuclear-encoded, mitochondrial enzyme that uses adenosylcobalamin as a cofactor. Biochemical cell studies have delineated phenotypic variants: mut(0) phenotypes in which there is no detectable enzymatic activity and mut- phenotypes in which there is residual cobalamin-dependent activity. Mutation screening in MMA has led to the detection of 30 disease-specific mutations. In 14 patients with the mut(0) phenotype we found 11 novel mutations (K54X, A137V, F174S, 620insA, G203R, Q218H, A535P, H627R, 2085delG and 2270del4/ins5), 6 of them homozygous, consisting of 1 nonsense, 6 missense, 1 splice site, and 3 frame shift mutations. The position in relation to different functional domains in MCM allow for an interpretation of the identified mutations. Hum Mutat 16:179, 2000.
Fuchshuber
A
A
University Children's Hospital, 79106 Freiburg, Germany. fuchshub@kkl200.ukl.uni-freiburg.de
Mucha
B
B
Baumgartner
E R
ER
Vollmer
M
M
Hildebrandt
F
F
D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics*; D008764:Methylmalonic Acid / Q000378:metabolism*; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
D008764:Methylmalonic Acid; D008765:Methylmalonyl-CoA Mutase