Molecular and structural analysis of two novel mutations in a patient with mut(-) methylmalonyl-CoA deficiency.
Inherited defects in the gene encoding the methylmalonyl-CoA mutase (MCM) result in the mut forms of methylmalonic aciduria (MMA). Twelve mutations have been identified associated with the mut(-) phenotype. We report two novel mutations (K621N and D156N) in a compound heterozygote mut(-) patient. These two mutations and three previously published ones (H627N, A191E, Y231N) were mapped onto a three-dimensional homology model of the human MCM constructed from the crystal structure of the Propionibacterium shermanii enzyme.
Benoist
J F
JF
Service de Biochimie-Hormonologie, Assitanace Publique-Hôpitaux de Paris, Hôpital Robert Debré, 48 Bd Sérurier, 75019 Paris, France. jean-francois.benoist@rdb.ap-hop-paris.fr
Acquaviva
C
C
Callebaut
I
I
Guffon
N
N
Ogier de Baulny
H
H
Mornon
J P
JP
Porquet
D
D
Elion
J
J
D000214:Acyl Coenzyme A / Q000737:chemistry* / Q000172:deficiency* / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D011424:Propionibacterium / Q000201:enzymology; D017434:Protein Structure, Tertiary
D000214:Acyl Coenzyme A; C015357:methylmalonyl-coenzyme A