Microdeletions at chromosome bands 1q32-q41 as a cause of Van der Woude syndrome

Van der Woude syndrome (VWS) is an autosomal dominant disorder comprising c left lip and/or cleft palate and lip pits. We reported previously a family whose underlying mutation is a 500-800 kb deletion localized to chromosome bands 1q32-q41 [Sander et al., 1994: Hum Mol Genet 3:576-578], Along with c left lip/palate and lip pits, affected relatives exhibit developmental dela ys, suggesting that the function of a gene nearby may also be disrupted. To further localize the VWS gene we searched for other deletions that cause V WS. An allele loss assay was performed using a novel highly polymorphic mar ker, D1S3753, From a panel of 37 unrelated individuals, we detected an alle le loss in one family, indicating the presence of a deletion. In this famil y, the phenotype in three generations of affected individuals was confined to the cardinal signs of VWS. Surprisingly, mapping of the new deletion sho wed that it extended 0.2-1 Mb beyond the proximal breakpoint for the deleti on described previously. No deletions were detected in seven cases of popli teal pterygia syndrome, 76 cases of mixed syndromic forms of cleft lip and palate, and 178 cases of nonsyndromic cleft lip and palate. These observati ons suggest that genetic searches for microdeletions should be routine in s creening patients for causes of VWS and may facilitate the positional cloni ng efforts of the VWS gene and of a nearby gene or genes that may be involv ed in brain development. Am. J, Med. Genet, 84:145-150, 1999. (C) 1999 Wile y-Liss, Inc.