title: Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders.
abstract: 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.
authors.affiliation: MRC Group in Medical Genetics, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Leclerc
authors.forename: E
authors.initials: E
authors.lastname: Campeau
authors.forename: P
authors.initials: P
authors.lastname: Goyette
authors.forename: C E
authors.initials: CE
authors.lastname: Adjalla
authors.forename: B
authors.initials: B
authors.lastname: Christensen
authors.forename: M
authors.initials: M
authors.lastname: Ross
authors.forename: P
authors.initials: P
authors.lastname: Eydoux
authors.forename: D S
authors.initials: DS
authors.lastname: Rosenblatt
authors.forename: R
authors.initials: R
authors.lastname: Rozen
authors.forename: R A
authors.initials: RA
authors.lastname: Gravel
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics* / Q000302:isolation & purification; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D014805:Vitamin B 12 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D006710:Homocysteine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12