Molecular genetics of methylenetetrahydrofolate reductase deficiency.
In severe MTHFR deficiency with neonatal or adolescent onset, 9 rare mutations have been identified. In mild MTHFR deficiency with thermolabile enzyme, a single common mutation (an alanine-to-valine substitution) is involved, but a genetic-nutrient interactive effect is required to produce mild hyperhomocysteinaemia. This interactive effect has been proposed to be a risk factor for arteriosclerosis and for neural-tube defects. Large-scale studies are required for confirmation of the role of MTHFR in these multifactorial processes as well as to assess its role in other folate-dependent disorders.
Department of Human Genetics, McGill University-Montreal Children's Hospital, Quebec, Canada.
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D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D018076:DNA, Complementary / Q000235:genetics; D014644:Genetic Variation; D006712:Homocystinuria / Q000150:complications / Q000201:enzymology / Q000235:genetics; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008967:Molecular Biology; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency* / Q000235:genetics*; D013696:Temperature
D018076:DNA, Complementary; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)