title: Identification of novel mutations of IRF6 gene in Chinese families with Van der Woude syndrome.
abstract: Van der Woude syndrome (VWS) is an autosomal dominant disorder of syndromic clefts clinically characterized by lower lip pits, cleft lip and/or palate, hypodontia. Mutations in the IRF6 gene have recently been found to cause VWS and more than 70 mutations have been reported. However, genotype distribution and prevalence of IRF6 mutations underlying Chinese are largely unknown. In the present study, we report on four Chinese families with VWS. Considerably variable clinical phenotypes were observed between and within each family. By direct sequencing, three novel mutations (Y111H, S407fsX436, F165fsX166) as well as a recurrent mutation (R400W) were identified. In contrast to the IRF6 mutations reported in Caucasians, the majority of these mutations occurred at a run of 1- or 2-base repetitive sequence unit, and localized neither in the conserved DNA-binding domain nor in the Smad-interferon regulatory factor-binding domain (SMIR). Therefore, our results indicate the existence of other putative IRF6 regions that are predisposed to mutations. Repeated nucleotides in the IRF6 coding regions may increase the instability and chance of DNA replication errors, and are prone to be potential mutation hot-spots.
authors.affiliation: Key Laboratory of Oral Biomedical Engineering of Ministry of Education, Department of Endocontics, Hospital and School of Stomatology, Wuhan University, Wuhan 430079, PR China.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Ye
authors.forename: Hui-Xi
authors.initials: HX
authors.lastname: Jin
authors.forename: Li-Song
authors.initials: LS
authors.lastname: Shi
authors.forename: Ming-Wen
authors.initials: MW
authors.lastname: Fan
authors.forename: Guang-Tai
authors.initials: GT
authors.lastname: Song
authors.forename: Hua-Li
authors.initials: HL
authors.lastname: Fan
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Bian
mesh_terms: D000848:Anodontia / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D013577:Syndrome
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors