Genetic studies in patients with nonsyndromic orofacial clefts

口面裂（唇裂和腭裂）是最常见的先天性畸形之一，可在各种复杂畸形综合征的背景下观察到。然而，约60%的病例被归类为非综合征性口面部唇裂。大量的流行病学研究结果表明，孤立性面部唇裂的病因是多因素的，其中有几种未知的相互作用的遗传机制。提出的研究的目的是确定遗传因素有助于发展的口面裂。我们打算收集100个家庭的DNA样本，每个家庭至少包括两个受影响的兄弟姐妹及其父母，300个三人组（一个受影响的孩子及其父母）和500名唇腭裂患者。招募计划是作为德国五个裂口中心的合作。在完成受影响的兄弟姐妹配对招募后，将对这些家庭进行系统的全基因组连锁分析。与抽样程序并行，候选基因的遗传变异将应用关联策略进行探索。对唇腭裂的遗传背景进行评估将有助于更好地了解其潜在的病理生理学，并可能促进特定的分子诊断、遗传咨询和预防或治疗方法。

Orofacial clefts (cleft lip and cleft palate) belong to one of the most common congenital anomalies and may be observed in the context of various complex malformation syndromes. However, about 60% of the cases are classified as nonsyndromic orofacial clefts. Results of numerous epidemiological studies point towards a multifactorial etiology of isolated facial clefts, with several unknown interacting genetic mechanisms. Aim of the proposed study is the identification of genetic factors contributing to the development of orofacial clefts. We intend to collect DNA samples of 100 families each comprising at least two affected siblings and their parents, 300 trios (one affected child and its parents), and 500 cleft patients. Recruitment is planned as a cooperation of five German cleft centers. After completion of affected sib-pair recruitment, a systematic genome-wide linkage analysis in these families will be employed. In parallel to the sampling procedure genetic variants of candidate genes will be explored applying association strategies. Evaluation of the genetic background of orofacial clefting will contribute to a better understanding of the underlying pathophysiology, and will possibly facilitate specific molecular diagnostics, genetic counseling and preventive or therapeutic approaches.