Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

Background: Folate metabolism dysfunctions can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) encoding gene (C677T and A1298C) reduce MTHFR activity, but when associated with aneuploidy, the results are conflicting. Turner syndrome (TS) is an interesting model for investigating the association between MTHFR gene polymorphisms and non disjunction because of the high frequency of chromosomal mosaicism in this syndrome. Aim: To investigate the association of MTHFR gene C677T and A1298C polymorphisms in TS girls and their mothers. To correlate these polymorphisms with maternal risk of TS offspring. Subjects and Methods: MTHFR C677T and A1298C polymorphisms were genotyped in 33 TS girls, their mothers and 15 healthy females with their mothers as controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing technique. Results: Genotype and allele frequencies of both C677T and A1298C were not significantly different between TS cases and controls. There were no significant differences in C677T genotype distribution between the TS mothers and controls (p=1). The MTHFR 1298AA and 1298AC genotypes were significantly increased in TS mothers Vs. control mothers (p=0.002). The C allele frequency of the A1298C polymorphism was significantly different between the TS mothers and controls (p=0.02). The association of A1298C gene polymorphism in TS girls was found to be increased with increasing age of both mothers and fathers of TS cases (p=0.026, 0.044) respectively. Conclusion: Our findings suggested a strong association between maternal MTHFR A1298C and risk of TS in Egypt

Issued also as CD