Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency.
Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene.
The diagnosis of MTHFR deficiency was confirmed based on extremely reduced fibroblast MTHFR activity (0.3 nmol CHO/mg prot/hr) as well as mutation analysis that revealed two variants in the MTHFR gene, a splice site mutation p (IVS5-1G>A), as well as a missense mutation (c.155 G>A; p. Arg52Gln).
In earlier work, we isolated the human cDNA for MTHFR, and reported 14 mutations in severe MTHFR deficiency, as well as a common 677C-->T missense mutation (Ala-->Val) that encodes the thermolabile MTHFR.
Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency.
A common variant in methylenetetrahydrofolate reductase (MTHFR677C→T) causes mild MTHFR deficiency with lower 5-methyltetrahydrofolate for methylation reactions.
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.
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.
To investigate the in vivo pathogenetic mechanisms of MTHFR deficiency, we generated mice with a knockout of MTHFR: Plasma total homocysteine levels in heterozygous and homozygous knockout mice are 1.6- and 10-fold higher than those in wild-type littermates, respectively.