目的 对2个中国范德伍德综合征(Van der Woude syndrome,VWS)家系进行临床和遗传特点分析,并进行IRF6基因的突变检测,明确中国人VWS致病基因IRF6的突变情况,并发现可疑的突变热点区域。方法 通过先证者及现场家系调查、临床检查和系谱分析收集2个VWS 家系成员24人的外周血样本,提取DNA用于IRF6基因的聚合酶链扩增反应(polymerase chain reaction,PCR)。采用Sanger测序法对所有VWS家系成员的IRF6基因的编码区7个外显子进行测序,使用mutation surveyor软件对测序结果与参考序列进行比对分析。结果 2个家系24人中受累患者6名,5名(83.3%)患者有唇腭裂,5名(83.3%)患者有唇瘘,6名患者均无牙齿发育不全表现,唇瘘伴唇腭裂表型常见,无其他组织器官畸形。24名成员均进行了IRF6基因第3至第9外显子的测序,6名患者均存在基因突变,家系1的3名患者均携带位于第9外显子的c.1234C>T杂合突变;家系2的3名患者均携带位于第9外显子的c.1210G>A杂合突变;未发现其他非患者的家系成员携带IRF6基因突变。结论 VWS综合征存在遗传异质性和临床表型复杂性,患者的表型与致病突变有关。通过基因检测可以对VWS患者进行遗传分析和产前诊断,弥补产前超声容易漏诊的不足。

Objective To investigate the clinical phenotype and IRF6 gene mutation in two Chinese kindred with Van der Woude syndrome (VWS),and understand the mutations of IRF6 and suspicious mutation hotspots in Chinese people. Methods The peripheral blood of 24 members from two VWS families were collected and directly performed the polymerase chain reaction (PCR) for screening the coding region of IRF6 gene.The soft ware of mutation surveyor was used to analysis the sequence. Results There were six VWS subjects in two families,5 (83.3%) patients had cleft lip and palate;5 (83.3%) patients had lip fistula.The results of IRF6 gene sequencing showed,six patients had mutations of IRF6 gene in 24 family members.The c.1234C>T heterozygous mutation was detected in 3 patients of family 1.In family 2,3 patients were carrying c.1210G> A heterozygous mutations.The other members of the families were wild type (wt/wt) for IRF6. Conclusions Based on these findings,the spectrum of mutations in IRF6 associated with VWS is extended.Genetic testing showed that cosegregated with the disease mutation.The identification of the role of IRF6 in VWS may help us to study any possible genotypephenotype relationship by combining molecular genetics.The mutations will play important role in genetic analysis and prenatal diagnosis of VWS.The ultrasound easily missed cleft palate,genetic testing can compensate for the lack of prenatal ultrasound.