HUMAN METHYLENETETRAHYDROFOLATE REDUCTASE - ISOLATION OF CDNA, MAPPING AND MUTATION IDENTIFICATION

Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for h omocysteine methylation to methionine. MTHFR deficiency, an autosomal recessive disorder, results in homocysteinemia. Using degenerate oligo nucleotides based on porcine peptide sequence data, we isolated a 90-b p cDNA by PCR from pig liver RNA. This cDNA was used to isolate a huma n cDNA, the predicted amino acid sequence of which shows strong homolo gy to porcine MTHFR and to bacterial metF genes. The human gene has be en localized to chromosome 1 p36.3. Two mutations were identified in M THFR-deficient patients: a missense mutation (Arg to Gln), in a residu e conserved in bacterial enzymes, and a nonsense mutation (Arg to Ter) .