Human Molecular Genetics, Vol 5, 1867-1874, Copyright © 1996 by Oxford University Press
D Leclerc, E Campeau, P Goyette, CE Adjalla, B Christensen, M Ross, P Eydoux, DS Rosenblatt, R Rozen and RA Gravel
Methionine synthase catalyzes the remethylation of homocysteine to
methionine in a methylcobalamin-dependent reaction. We used specific
regions of homology within the methionine synthase sequences of several
lower organisms to clone a human methionine synthase cDNA by a combination
of RT-PCR and inverse PCR. The enzyme is 1265 amino acids in length and
contains the seven residue structure-based sequence fingerprint identified
for cobalamin-containing enzymes. The gene was localized to chromosome 1q43
by the FISH technique. We have identified one missense mutation and a 3 bp
deletion in patients of the cblG complementation group of inherited
homocysteine/folate disorders by SSCP and sequence analysis, as well as an
amino acid substitution present in high frequency in the general
population. We discuss the possibility that a mild deficiency of methionine
synthase activity could be associated with mild hyperhomocysteinemia, a
risk factor for cardiovascular disease and possibly neural tube defects.
ARTICLES
Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders
MRC Group in Medical Genetics, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
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