Genetic studies in patients with nonsyndromic orofacial clefts

口腔颌面裂(唇裂和腭裂)属于最常见的先天畸形之一，可在各种复杂的畸形综合征中观察到。然而，约60%的病例被归类为非综合征性口面部裂。大量流行病学研究的结果表明，孤立性面裂的病因是多因素的，有几个未知的相互作用的遗传机制。这项拟议的研究的目的是确定导致口裂发生的遗传因素。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(一个受影响的儿童及其父母)，以及500名唇裂患者。招募计划由五个德国唇裂中心合作完成。在完成受影响的同胞对招募后，将在这些家系中进行系统的全基因组连锁分析。在抽样程序的同时，将应用关联策略来探索候选基因的遗传变异。评估口腔裂隙的遗传背景将有助于更好地了解潜在的病理生理学，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.