A Founder Mutation Causing a Severe Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in Bukharian Jews
Mol Genet Metab. 2012 Nov;107(3):608-10
Homocystinuria due to methylenetetrahydrofolate reductase (MTHFR) deficiency (OMIM ID: 236250) is a rare inborn error of folate metabolism resulting in elevated homocysteine levels in plasma and urine . Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. The severe form of the disease is characterized by developmental delay, seizures and microcephaly , and may be associated with infantile epilepsy . The disease is autosomally recessively inherited, caused by mutations in the MTHFR gene . It has been suggested that early treatment with betaine may alleviate the effect of the disease to the brain in some cases . In this study we demonstrate the existence of a common splicing founder mutation in the MTHFR gene, causing a severe MTHFR deficiency among individuals of Jewish Bukharic ancestry.