Nature Genetics
7, 195 - 200 (1994)
doi:10.1038/ng0694-195
Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identificationPhilippe Goyette1, James S. Sumner2, Renate Milos1, Alessandra M.V. Duncan3, David S. Rosenblatt1, 4, Rowena G. Matthews2
& Rima Rozen1
1Departments of Pediatrics, Human Genetics, and Biology McGill University - Montreal Children's Hospital Research Institute, 2300 Tupper, Montreal, Quebec H3H 1P3, Canada
2Biophysics Research Division and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109−1055, USA
3Queen's University and Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada
4Department of Medicine, McGill University, Montreal Quebec H3A 1A1, Canada Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for homocysteine methylation to methionine. MTHFR deficiency, an autosomal recessive disorder, results in homocysteinemia. Using degenerate oligonucleotides based on porcine peptide sequence data, we isolated a 90−bp cDNA by PCR from pig liver RNA. This cDNA was used to isolate a human cDNA, the predicted amino acid sequence of which shows strong homology to porcine MTHFR and to bacterial metF genes. The human gene has been localized to chromosome 1p36.3. Two mutations were identified in MTHFR−deficient patients: a missense mutation (Arg to Gin), in a residue conserved in bacterial enzymes, and a nonsense mutation (Arg to Ter).
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