title: Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.
abstract: Methylenetetrahydrofolate reductase (MTHFR) is the only route for the synthesis of 5-methyltetrahydrofolate, which is utilized to convert homocysteine to methionine. In this study, we measured the enzyme activity of a mutant MTHFR that was detected in a patient with hyperhomocysteinemia. The 428C>T mutation in exon 2 of the MTHFR gene is a novel mutation, while the [458G>T+459C>T] mutation in exon 2 is a previously reported mutation. The activity of mutant enzymes containing the 428C>T, [458G>T+459C>T] and 677C>T mutations was 12.7+/-4.7%, 48.1+/-18.8%, and 43.6+/-14.4%, respectively, of that of the wild type enzyme. Our results suggest that these two variants each result in a severe MTHFR deficiency, which causes a developmental delay and cerebral vascular disease.
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishimachi, 683-8504, Yonago, Japan. hydeta@grape.med.tottori-u.ac.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaso
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yasui
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Wakutani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayasu
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kowa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D002658:Developmental Disabilities / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics* / Q000378:metabolism; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)