Genetic studies in patients with nonsyndromic orofacial clefts

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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.