title: Two missense mutations of the IRF6 gene in two Japanese families with popliteal pterygium syndrome.
abstract: Mutations in the interferon regulatory factor 6 gene (IRF6) cause either popliteal pterygium syndrome (PPS) or Van der Woude syndrome (VWS), allelic autosomal dominant orofacial clefting conditions. To further investigate the IRF6 mutation profile in PPS, we performed mutation analysis of patients from two unrelated Japanese families with PPS and identified mutations in IRF6: c.251G>T (R84L) and c.1271C>T (S424L). We also found R84L, which together with previous reports on R84 mutations, provided another line of evidence that both syndromes could result from the same mutation probably under an influence of a modifier gene(s). This supports the idea that the R84 residue in the DNA binding domain of IRF6 is a mutational hot spot for PPS. A luciferase assay of the S424L protein in the other family demonstrated that the mutation decreased the IRF6 transcriptional activity significantly to 6% of that of the wild-type. This finding suggests that the C-terminus region of IRF6 could have an important function in phosphorylation or protein interaction. To our knowledge, this is the first report of mutations observed in Japanese PPS patients.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okazaki City Hospital, Okazaki, Japan. mnoriko51@yahoo.co.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Matsuzawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Kondo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimozato
authors.forename: Toru
authors.initials: T
authors.lastname: Nagao
authors.forename: Motoi
authors.initials: M
authors.lastname: Nakano
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tsuda
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirano
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.forename: Koh-Ichiro
authors.initials: K
authors.lastname: Yoshiura
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D044466:Asian People; D001665:Binding Sites; D002971:Cleft Lip / Q000235:genetics; D002972:Cleft Palate / Q000235:genetics; D003560:Cysts / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D006801:Humans; D007223:Infant; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008046:Lip / Q000002:abnormalities; D008297:Male; D020125:Mutation, Missense; D010766:Phosphorylation; D011485:Protein Binding; D011625:Pterygium / Q000235:genetics*
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors