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

Overview

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 date

  • December 1, 1996

Research

keywords

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • Amino Acid Metabolism, Inborn Errors
  • Chromosomes, Human, Pair 1
  • DNA, Complementary
  • Homocysteine
  • Vitamin B 12

Identity

Scopus Document Identifier

  • 10544249877

Digital Object Identifier (DOI)

  • 10.1093/hmg/5.12.1867

PubMed ID

  • 8968737

Additional Document Info

volume

  • 5

issue

  • 12