Abstract
Mice with a deletion of Tgf-β3 (−/−) and association studies in humans of different ethnicities support the involvement of TGFB3 in the etiology of orofacial clefts. In this study, we investigated the relevance of TGFB3 in the development of cleft lip and palate (CL/P) among 204 triads of central European origin. Transmission-disequilibrium test (TDT) analysis revealed no significant transmission distortions for each marker alone, and none for any possible haplotypes. However, we found strong evidence for parent-of-origin effects, with lower risk of maternal transmission compared with paternal transmission [I M = 0.38; confidence interval (CI): 0.17–0.86] of the risk allele T to an affected offspring at marker rs2300607. This is also expressed in an increased risk of heterozygous children having the T allele inherited from the father (R P = 3.47; CI: 1.32–9.11). Our data support the involvement of TGFB3 in the development of oral clefts in patients of central European origin.
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Acknowledgments
We thank all participants for consenting to the study and providing blood samples. We are grateful to Birgit Kroschel-Lang, Charlotte Opitz, Michael Krimmel, and the German Support Group for People with Cleft Lip and/or Palate (Selbsthilfevereinigung für Lippen-Gaumen-Fehlbildungen e.V. Deutschland) for kind support in contacting patients. The authors also thank Susanne Raeder for skilful help with laboratory work. This study was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) to EM and FJK (FOR 423 Genetic Epidemiology and Medical Genetics of Complex Diseases, Project N1).
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Reutter, H., Birnbaum, S., Mende, M. et al. TGFB3 displays parent-of-origin effects among central Europeans with nonsyndromic cleft lip and palate. J Hum Genet 53, 656–661 (2008). https://doi.org/10.1007/s10038-008-0296-9
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DOI: https://doi.org/10.1007/s10038-008-0296-9
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