Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders

Hum Mol Genet. 1996 Dec;5(12):1867-74. doi: 10.1093/hmg/5.12.1867.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics*
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / metabolism
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1*
  • Cloning, Molecular
  • DNA, Complementary / genetics*
  • DNA, Complementary / isolation & purification
  • Homocysteine / blood*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Sequence Alignment
  • Vitamin B 12 / genetics
  • Vitamin B 12 / metabolism*

Substances

  • DNA, Complementary
  • Homocysteine
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • Vitamin B 12

Associated data

  • GENBANK/U71285