title: TGFB3 displays parent-of-origin effects among central Europeans with nonsyndromic cleft lip and palate.
abstract: Mice with a deletion of Tgf-beta3 (-/-) 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.
authors.affiliation: Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, 53111, Bonn, Germany. reutter@uni-bonn.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.affiliation: Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, 53111, Bonn, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Birnbaum
authors.affiliation: Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Meinhard
authors.initials: M
authors.lastname: Mende
authors.affiliation: Department of Cleft Lip and Cleft Palate Surgery, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Lauster
authors.affiliation: Department of Cleft Lip and Cleft Palate Surgery, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Gül
authors.initials: G
authors.lastname: Schmidt
authors.affiliation: Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Henschke
authors.affiliation: Department of Orthodontics, University of Cologne, Cologne, Germany.
authors.forename: Mitra
authors.initials: M
authors.lastname: Saffar
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University of Bonn, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Martini
authors.affiliation: Molecular Biology, German Arthritis Research Centre, Berlin, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Lauster
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schiefke
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University of Bonn, Bonn, Germany.
authors.forename: Rudolf H
authors.initials: RH
authors.lastname: Reich
authors.affiliation: Department of Orthodontics, University of Cologne, Cologne, Germany.
authors.forename: Bert
authors.initials: B
authors.lastname: Braumann
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University of Cologne, Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Scheer
authors.affiliation: Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.affiliation: Department of Genomics, Life and Brain Centre, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University of Göttingen, Göttingen, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Kramer
authors.affiliation: Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, 53111, Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
mesh_terms: D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005060:Europe; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D010159:Palate / Q000002:abnormalities*; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D053782:Transforming Growth Factor beta3 / Q000235:genetics*
chemical_list: C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3