Genetic heterogeneity and exclusion of a modifying locus at 17p11.2-p11.1 in Finnish families with van der Woude syndrome

Editor—The van der Woude syndrome (VWS, OMIM 119300) is the most common form of syndromic cleft lip and palate, affecting 1/30 000 of the general population.1 The syndrome is inherited in an autosomal dominant fashion with almost complete penetrance.2 The clinical features of VWS include paramedial pits on the lower lip, cleft lip with or without cleft palate, cleft palate, and hypodontia. However, the presence and severity of the individual features is highly variable within and between families.3 A constitutional interstitial deletion of chromosome 1q32-q41 was first described by Bocian and Walker4 in a patient with lip pits. Linkage of VWS to this locus was then established by Murray et al 5 and subsequently Schutte et al 6 refined the locus to a 1.6 cM region between D1S491 and D1S205. Recently, a microdeletion test using a novel polymorphic marker D1S3753 derived from the VWS critical region was also used.7 To date, 1q32-q41 is the only locus described for VWS and the VWS gene has yet to be identified. Recently, a large Brazilian VWS family with multiple cases affected with cleft palate was studied by Sertie et al .8 Linkage analysis was performed to search for a modifying locus for the cleft palate phenotype and suggestive linkage was shown in chromosome 17p11.2-p11.1 with a maximum lod score of 2.05 at D17S1824. The authors proposed the region as a modifying locus for cleft palate in VWS. The homogeneous nature of the Finnish population is conducive for genetic studies especially for linkage disequilibrium analysis.9 The clinical features of Finnish VWS patients have previously been described,1 10 but no genetic studies have been reported. In this study, five Finnish VWS families were tested for linkage to the 1q32-q41 region and to the proposed modifying locus …