A genome-wide scan for loci predisposing to non-syndromic cleft lip with or without cleft palate in two large Syrian families

Non-syndromic cleft lip with/without cleft palate (CL/P) is a common, usually non-fatal birth defect of complex etiology. Several segregation analyses have demonstrated that genetic factors are important in the pathogenesis of CL/P, most likely through the interaction of several genes of modest effects. The aim of this study was to perform a genome-wide linkage analysis to identify/search for candidate gene loci for CL/P. We conducted a genome-wide search in two large, relatively isolated Syrian families, each one with a large number of cases with CL/P (18 in family 1 and 4 in family 2). A locus with a multipoint LOD score of 2.80 and a 2-point non-parametric MLS LOD of 3.0 was detected on 17p13.1. Other chromosomal regions with multipoint LOD scores greater than or equal to1.2 (P less than or equal to 0.01) included 3p21.2, 4q32.1, and 7q34. These data indicate the possible presence of several susceptibility loci for CL/P and identify a strong candidate locus for this common birth defect on chromosome 17p13. Published 2003 Wiley-Liss, Inc(dagger).