Transforming growth factor-alpha and nonsyndromic cleft lip with or without palate in Brazilian patients: results of a large case-control study.

Objective: Transforming growth factor-alpha (TGFA) was the first gene suggested to be associated with nonsyndromic cleft lip, cleft palate, or both (CL/ P). There are, however, still controversies of the effect of TGFA on the predisposition of this malformation. To contribute to a better understanding of the role of this gene in the occurrence of CL/P we undertook a case-control study including patients and controls ascertained in different regions of the country.

Maternal MTHFR interacts with the offspring's BCL3 genotypes, but not with TGFA, in increasing risk to nonsyndromic cleft lip with or without cleft palate.

The 677 C --> T polymorphism in the 5-10 methylenetetrahydrofolate reductase (MTHFR) gene has been associated with nonsyndromic cleft lip with or without cleft palate (CL/P) in some populations, but not others. Previous studies (ie, case-control and transmission disequilibrium tests (TDT)) in Brazilian families with CL/P have been unable to replicate this putative association. However, our group observed a lower proportion of CT heterozygotes among the mothers of CL/P probands, suggesting that the maternal genotype for this polymorphism might influence predisposition to CL/P.