Mutation analysis of the MMAA and MMAB genes in Japanese patients with vitamin B(12)-responsive methylmalonic acidemia: identification of a prevalent MMAA mutation.
Methylmalonic acidemia (MMA) is caused by the deficient activity of l-methylmalonyl-CoA mutase, which is a vitamin B(12) (or cobalamin, Cbl)-dependent enzyme. MMA due to the effect of insufficient Cbl metabolism is classified into three forms (cblA, cblB, and cblH). Recently, the genes responsible for cblA and cblB were identified as MMAA and MMAB, respectively. The MMAA protein likely transports Cbl into the mitochondria for adenosylcobalamin synthesis, while the MMAB protein appears to be an adenosyltransferase. We performed a mutation analysis of 10 unrelated Japanese patients with vitamin B(12)-responsive MMA. Seven patients had mutations in MMAA, whereas the other three patients showed no disease-causing substitutions in either MMAA or MMAB. Five novel mutations were identified in MMAA (R22X, R145X, L217X, R359G, and 503delC). The 503delC mutation was observed in five of the seven MMAA patients, suggesting that the mutation is prevalent in Japanese patients. This finding may facilitate the DNA diagnosis of vitamin B(12)-responsive MMA within the Japanese population.
Department of Medical Genetics, Tohoku University School of Medicine, Japan.
Xue
X
Yang
Osamu
O
Sakamoto
Yoichi
Y
Matsubara
Shigeo
S
Kure
Yoichi
Y
Suzuki
Yoko
Y
Aoki
Yasuyuki
Y
Suzuki
Nobuo
N
Sakura
Masaki
M
Takayanagi
Kazuie
K
Iinuma
Toshihiro
T
Ohura
D000138:Acidosis / Q000208:ethnology / Q000235:genetics*; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D007564:Japan; D026901:Membrane Transport Proteins / Q000235:genetics*; D008765:Methylmalonyl-CoA Mutase / Q000172:deficiency*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D013577:Syndrome; D014805:Vitamin B 12 / Q000378:metabolism
C497512:MMAA protein, human; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D019883:Alkyl and Aryl Transferases; C019920:cob(I)alamin adenosyltransferase; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12