Sertié A L, Sousa A V, Steman S, Pavanello R C, Passos-Bueno M R
Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, 277, 05508-900, São Paulo, Brazil.
Am J Hum Genet. 1999 Aug;65(2):433-40. doi: 10.1086/302491.
van der Woude syndrome (VWS), which has been mapped to 1q32-41, is characterized by pits and/or sinuses of the lower lip, cleft lip/palate (CL/P), cleft palate (CP), bifid uvula, and hypodontia (H). The expression of VWS, which has incomplete penetrance, is highly variable. Both the occurrence of CL/P and CP within the same genealogy and a recurrence risk <40% for CP among descendants with VWS have suggested that the development of clefts in this syndrome is influenced by modifying genes at other loci. To test this hypothesis, we have conducted linkage analysis in a large Brazilian kindred with VWS, considering as affected the individuals with CP, regardless of whether it is associated with other clinical signs of VWS. Our results suggest that a gene at 17p11.2-11.1, together with the VWS gene at 1p32-41, enhances the probability of CP in an individual carrying the two at-risk genes. If this hypothesis is confirmed in other VWS pedigrees, it will represent one of the first examples of a gene, mapped through linkage analysis, which modifies the expression of a major gene. It will also have important implications for genetic counseling, particularly for more accurately predicting recurrence risks of clefts among the offspring of patients with VWS.
范德伍德综合征（VWS）已被定位到1q32 - 41，其特征为下唇凹陷和/或窦道、唇腭裂（CL/P）、腭裂（CP）、悬雍垂裂和牙齿发育不全（H）。VWS的表现具有不完全外显率，且高度可变。在同一家系中同时出现CL/P和CP，以及VWS患者后代中CP的复发风险<40%，这表明该综合征中腭裂的发生受其他位点修饰基因的影响。为了验证这一假设，我们对一个患有VWS的大型巴西家系进行了连锁分析，将患有CP的个体视为患病个体，无论其是否与VWS的其他临床体征相关。我们的结果表明，位于17p11.2 - 11.1的一个基因，与位于1p32 - 41的VWS基因一起，增加了携带这两个风险基因的个体发生CP的概率。如果这一假设在其他VWS家系中得到证实，它将代表通过连锁分析定位的首个修饰主基因表达的基因实例之一。这对于遗传咨询也将具有重要意义，特别是对于更准确地预测VWS患者后代腭裂的复发风险。
