A Novel Homozygous Non-sense Mutation in the Catalytic Domain of MTHFR Causes Severe 5,10-Methylenetetrahydrofolate Reductase Deficiency

Conclusion: We identified a novel non-sense mutation in MTHFR gene in a single Egyptian family with severe MTHFR deficiency. The present investigation is clinically important, as it adds to the growing list of MTHFR mutations, which might help in genetic counseling of families of affected children and proper genotype-phenotype correlation. Background Severe 5,10-Methylenetetrahydrofolate reductase (MTHFR; OMIM 236250) deficiency is a rare inborn error of metabolism and inherited in an autosomal recessive fashion. It is a very common disorder of folate metabolism and is clinically characterized with low plasma methionine level, high homocysteine level, homocystinuria, and hyperhomocysteinemia (1, 2). MTHFR gene is responsible for the assembly of MTHFR enzyme, which plays a very important role in the catalysis of 5,10-methyltetrahydrofolate (THF) to 5-methyltetrahydrofolate (an NADPH-dependent irreversible reduction) to obtain methionine from homocysteine (Supplementary Figure 1). Methyl THF is the most common form of folate in tissues and the plasma and serves as the methyl group donor in the methyl THF-homocysteine S-methyltransferase reaction involving remethylation of homocysteine to methionine (3). The deficiency of MTHFR enzyme causes an increase in the concentration of homocysteine and methionine, resulting in severe neurological phenotypes. Patients having neonatal onset (i.e., early onset <1-year-old) MTHFR deficiency are mostly associated with feeding ...
Source: Frontiers in Neurology - Category: Neurology Source Type: research