一个范德伍德综合征家系的IRF6基因突变检测

目的:对收集的1个湖北Van der Woude综合征(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。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VWS家系。在IRF6基因的外显子-内含子接头及9个外显子编码区分别设计引物,经聚合酶链式反应扩增并纯化后直接测序。结果:收集的VWS家系符合常染色体显性遗传特征,家系受累患者共3名(1名男性和2名女性),患者表现为典型的下唇瘘管或凹陷,且合并有唇腭裂和先天缺牙。患者表型在同一家系内有明显差异,且呈逐代加重趋势。在所有患者IRF6基因第412位密码子发现与表型一致的CGA>TGA(c.1234C>T)改变,经查证为一个已知的无义突变。结论:该VWS家系疾病表现度极不一致,是由IRF6基因的1个已知无义突变导致,IRF6是参与颌面部发育的重要基因。

Mutation Analysis of a Chinese Kindred with Van der Woude Syndrome

Objective: To investigate the clinical phenotype and IRF6 gene mutation in a Chinese kindred with van der Woude syndrome. Methods: Pedigree was collected through probands and family members were interviewed. Oral examinations and clinical manifestations were analysed. PCR and DNA sequencing were employed to detect the mutation of IRF6 gene. Results: Of the family investigated, an autosomal dominant inheritance mode was suggested. 3 patients were examined (1 male, 2 female). Most patients had typical lower lip pits or sinuses, together with cleft lip with or without cleft palate, and hypodontia. The phenotype varied considerablely within the family, and the descents often showed full-blown symptoms. A CGA>TGA(c.1234C>T)transversion of IRF6 was identified in codon 412, and was segregated with the disease phenotypes. Conclusion: This VWS family transmitted in an autosomal dominant mode with highly variable expressivity, and was associated with IRF6 gene nonsense mutation. IRF6 gene participated an important role in the craniofacial development.