title: Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian Turner Syndrome patients.
abstract: 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 nondisjunction because of the high frequency of chromosomal mosaicism in this syndrome.
  
  
  OBJECTIVE
  To investigate the association of MTHFR gene C677T and A1298C polymorphisms in TS patients and their mothers and to correlate these polymorphisms with maternal risk of TS offspring.
  
  
  METHODS
  MTHFR C677T and A1298C polymorphisms were genotyped in 33 TS patients, 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 patients was found to increase with increasing age of both mothers (p=0.026) and fathers (p=0.044) of TS cases.
  
  
  CONCLUSIONS
  Our findings suggest a strong association between maternal MTHFR A1298C and risk of TS in Egypt.
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Manal F
authors.initials: MF
authors.lastname: Ismail
authors.affiliation: Department of Molecular Genetics, National Research Centre, Cairo, Egypt.
authors.forename: Waheba A
authors.initials: WA
authors.lastname: Zarouk
authors.affiliation: Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
authors.forename: Mona O
authors.initials: MO
authors.lastname: Ruby
authors.affiliation: Department of Cytogenetics, National Research Centre, Cairo, Egypt.
authors.forename: Wael M
authors.initials: WM
authors.lastname: Mahmoud
authors.affiliation: Department of Molecular Genetics, National Research Centre, Cairo, Egypt.
authors.forename: Randa S
authors.initials: RS
authors.lastname: Gad
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007621:Karyotyping; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D014424:Turner Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)