Evidence for a microdeletion in 1q32-41 involving the gene responsible for Van der Woude syndrome

Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder representing the most frequent form of syndromic cleft lip and palate. Other characteristic features are pits of the lower lip and hypodontia. The gene shows high penetrance and seems to play an important role in orofacial development determined by the tissues involved and their formation during different periods of craniofacial development. Although most individuals affected with VWS show Mendelian inheritance, one patient with a macroscopic deletion and multiple malformations including two primary features of VWS has been described in the literature, indicating hemizygosity is compatible with the VWS phenotype. We report here the allelic loss of a stable and highly polymorphic microsatellite (D1S205) from region 1q32-41 in one family with VWS. Classical manifestations of the syndrome superimposed on developmental delay in all affected members of the family, the absence of cytogenetic abnormalities, the reproducibility of the null allele with a new set of primers and close linkage of this marker in a total of 15 VWS families provide strong evidence that the first microdeletion involving the gene for VWS has been identified. Assuming 1 Mb of DNA per cM of genetic distance, the upper bound of the deletion size would amount to 4 Mb.