Gene identification for the cblD defect of vitamin B12 metabolism.

摘要: BACKGROUND: Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin mitochondria and methylcobalamin the cytoplasm, necessary for homeostasis methylmalonic acid homocysteine. Nine defects intracellular metabolism have been defined by means somatic complementation analysis. One these defects, cblD defect, can cause isolated aciduria, homocystinuria, or both. Affected persons present with multisystem clinical abnormalities, including developmental, hematologic, neurologic, findings. The gene responsible defect has not identified. METHODS: We studied seven patients skin fibroblasts from each were investigated cell culture. Microcell-mediated chromosome transfer refined genetic mapping used localize gene. This was transfected into test rescue synthesis. RESULTS: localized human 2q23.2, a candidate gene, designated MMADHC (methylmalonic type, homocystinuria), identified this region. Transfection wild-type rescued cellular phenotype, functional importance mutant alleles shown transfection constructs. predicted protein sequence homology bacterial ATP-binding cassette transporter contains putative binding motif mitochondrial targeting sequence. CONCLUSIONS: Mutations we are vitamin metabolism. Various mutations associated three biochemical phenotypes disorder.