PMID- 9781030 OWN - NLM STAT- MEDLINE DCOM- 19981104 LR - 20061115 IS - 1018-4813 (Print) IS - 1018-4813 (Linking) VI - 6 IP - 3 DP - 1998 May-Jun TI - Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. PG - 257-65 AB - Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is an inborn error of folate metabolism, and is inherited as an autosomal recessive trait. MTHFR is a key enzyme in folate-dependent remethylation of homocysteine, and reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Patients with this severe enzymatic deficiency are biochemically characterised by homocystinuria and hypomethioninaemia, and may suffer from neurological abnormalities, mental retardation and premature vascular disease. Here we report the molecular basis of severe MTHFR deficiency in four unrelated families from Turkish/Greek ancestry. By use of reverse-transcriptase (RT)-PCR, subsequently followed by direct sequencing analysis, we were able to identify four novel mutations in the MTHFR gene: two missense (983A-->G; 1027T-->G) and two nonsense (1084C-->T; 1711C-->T) mutations. Furthermore, a splice variant containing a premature termination codon, was observed in one patient, probably as a secondary effect of the 1027T-->G missense mutation. The ongoing identification and characterisation of mutations in the MTHFR gene will provide further insight into the heterogeneity of the clinical phenotype in severe MTHFR deficiency. FAU - Kluijtmans, L A AU - Kluijtmans LA AD - Department of Pediatrics, University Hospital Nijmegen, The Netherlands. FAU - Wendel, U AU - Wendel U FAU - Stevens, E M AU - Stevens EM FAU - van den Heuvel, L P AU - van den Heuvel LP FAU - Trijbels, F J AU - Trijbels FJ FAU - Blom, H J AU - Blom HJ LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Hum Genet JT - European journal of human genetics : EJHG JID - 9302235 RN - 0 (DNA Primers) RN - EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors) RN - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2)) SB - IM MH - Amino Acid Sequence MH - Base Sequence MH - Child MH - DNA Primers MH - Female MH - Humans MH - Metabolism, Inborn Errors/*genetics MH - Methylenetetrahydrofolate Reductase (NADPH2) MH - Molecular Sequence Data MH - *Mutation MH - Oxidoreductases Acting on CH-NH Group Donors/deficiency/*genetics MH - Sequence Homology, Amino Acid EDAT- 1998/10/22 00:00 MHDA- 1998/10/22 00:01 CRDT- 1998/10/22 00:00 PHST- 1998/10/22 00:00 [pubmed] PHST- 1998/10/22 00:01 [medline] PHST- 1998/10/22 00:00 [entrez] AID - 10.1038/sj.ejhg.5200182 [doi] PST - ppublish SO - Eur J Hum Genet. 1998 May-Jun;6(3):257-65. doi: 10.1038/sj.ejhg.5200182.