| Abstract |
Vitamin B12 (cobalamin, Cbl) is an essential coenzyme in mammals for two
reactions: the conversion of homocysteine to methionine by the enzyme
methionine synthase and the conversion of methylmalonyl-CoA to succinyl-
CoA by the enzyme methylmalonyl-CoA mutase. In cells, cobalamin is
converted to the two active coenzyme forms of the vitamin: methylcobalamin
and 5'-deoxyadenosylcobalamin. Eight groups of patients have been
described with intracellular disorders of cobalamin metabolism, named cblA-
cblG and mut. Three groups of patients present with an inability to
produce both methylcobalamin and 5'deoxyadenosylcobalamin: cblF, cblC and
cblD. We located the gene responsible for the cblF type of cobalamin
disorder to chromosome 6 by microcell-mediated chromosome transfer,
leading to the discovery of the LMBRD1 gene. We identified three novel
mutations in LMBRD1 among cblF patients. We reviewed phenotypic and
genetic data on three cblD patients and were able to confirm previous
genotype-phenotype correlations. We purified the MMADHC protein defective
in the cblD group of cobalamin disorder and predicted that interactions
with the protein defective in the cblC group occur in a domain homologous
to a bacterial domain involved also in protein-protein interactions.
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