QJM, Vol 90, Issue 8 511-517, Copyright © 1997 by Oxford University Press
NM van der Put, EF van der Molen, LA Kluijtmans, SG Heil, JM Trijbels, TK Eskes, D Van Oppenraaij-Emmerzaal, R Banerjee and HJ Blom
Elevated homocysteine (Hcy) levels are observed in two apparently unrelated
diseases: neural-tube defects (NTD) and premature vascular disease.
Defective human methionine synthase (MS) could result in elevated Hcy
levels. We sequenced the coding region of MS in 8 hyperhomocysteinaemic
patients (4 NTD patients and 4 patients with pregnancies complicated by
spiral arterial disease, SAD). We identified only one mutation resulting in
an amino acid substitution: an A-->G transition at bp 2756, converting
an aspartic acid (D919) into a glycine (G). We screened genomic DNA for the
presence of this mutation in 56 NTD patients, 69 mothers of children with
NTD, 108 SAD patients and 364 controls. There was no increased prevalence
of the GG and AG genotypes in NTD patients, their mothers or SAD patients.
The D919G mutation does not seem to be a risk factor for NTD or vascular
disease. We then examined the mean Hcy levels for each MS genotype. There
was no correlation between GG- or AG-genotype and Hcy levels. The D919G
mutation is thus a fairly prevalent, and probably benign polymorphism. This
study, though limited, provides no evidence for a major involvement of MS
in the aetiology of homocysteine-related diseases such as NTD or vascular
disease.
ORIGINAL PAPERS
Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease
Department of Pediatrics, University Hospital Nijmegen, The Netherlands.
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