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RESEARCH REPORT |
1 Departments of Pediatrics, 2613 JCP,
2 Biological Sciences, and
3 Genetics PhD Program, University of Iowa, 200 Hawkins Drive, W229-1 GH, Iowa City, IA 52242-1083, USA;
4 Latin American Collaborative Study of Congenital Malformations (ECLAMC) at Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil;
5 Latin American Collaborative Study of Congenital Malformations (ECLAMC) at Department of Genetics, Oswaldo Cruz Institute, Rio de Janeiro, RJ, Brazil, and CEMIC, Buenos Aires, Argentina;
6 Center for Craniofacial and Dental Genetics, School of Dental Medicine, and Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA;
7 Bolsista da CAPES, Brasilia, Brazil;
*corresponding author, jeff-murray{at}uiowa.edu
MSX1 and TGFB3 have been proposed as genes in which mutations may contribute to non-syndromic forms of oral clefts; however, an interaction between these genes has not been described. The present study attempts to detect transmission distortion of MSX1 and TGFB3 in 217 South American children from their respective mothers. With transmission disequilibrium test analysis, cleft lip with/without cleft palate, cleft lip with palate plus cleft palate only, and all datasets combined showed evidence of association with MSX1 (p = 0.004, p = 0.037, and p = 0.001, respectively). With likelihood ratio test analysis, "cleft lip only" showed association with MSX1 (p = 0.04) and "cleft palate only" with TGFB3 (p = 0.02). A joint analysis of MSX1 and TGFB3 suggested that there may be an interaction between these two loci to increase cleft susceptibility. These results suggest that MSX1 and TGFB3 mutations make a contribution to clefts in South American populations.
KEY WORDS: cleft lip and palate • cleft palate • MSX1 • TGFB3 • ECLAMC
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