C677T variant form at the MTHFR gene and CL/P: A risk factor for mothers?

M. Martinelli, L. Scapoli, F. Pezzetti, F. Carinci, P. Carinci, G. Stabellini, L. Bisceglia, F. Gombos, M. Tognon

Research output: Contribution to journalArticlepeer-review


Maternal folic acid supplementation in early pregnancy has been suggested to play a role in the prevention of nonsyndromic orofacial cleft, i.e., cleft lip with or without cleft palate (CL/P). Moreover, some authors demonstrated association of the C→T mutation (C677T), converting an alanine to a valine residue in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with other congenital anomalies such as neural tube defects (NTDs). Because of MTHFR's involvement in the metabolism of folate, we investigated 64 CL/P patients and their parents for C677T MTHFR mutation. No linkage disequilibrium was found using the transmission disequilibrium test (TDT). However, a significantly higher mutation frequency was detected in mothers of CL/P patients compared to controls. The odds ratios calculated for mothers having CT or TT genotype, compared to the normal CC genotype, were 2.75 (95% confidence interval 1.30-5.57) and 2.51 (1.00-6.14), respectively. These results support the involvement of the folate pathway in the etiology of CL/P, and indicate an effect of the maternal genotype, rather than influence of the embryo's genotype.

Original languageEnglish
Pages (from-to)357-360
Number of pages4
JournalAmerican Journal of Medical Genetics
Issue number4
Publication statusPublished - Feb 1 2001


  • 5,10-methylenetetrahydrofolate reductase
  • Cleft lip with or without cleft palate
  • Orofacial cleft

ASJC Scopus subject areas

  • Genetics(clinical)


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