A Founder Mutation Causing a Severe Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in Bukharian Jews

Mol Genet Metab. 2012 Nov;107(3):608-10
doi: 10.1016/j.ymgme.2012.08.011

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 [1]. 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 [2], and may be associated with infantile epilepsy [3]. The disease is autosomally recessively inherited, caused by mutations in the MTHFR gene [4]. It has been suggested that early treatment with betaine may alleviate the effect of the disease to the brain in some cases [5]. 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.


  • Shay Ben-Shachar , MD
  • Tal Zvi
  • Prof. Arndt Rolfs , MD
  • Andrea Breda Klobus , MD
  • Yuval Yaron , MD
  • Anat Bar-Shira , PhD
  • Avi Orr-Urtreger , PhD