Two Missense Mutations of the IRF6 Gene in Two Japanese Families With Popliteal Pterygium Syndrome
Two Missense Mutations of the IRF6 Gene in Two Japanese Families With Popliteal Pterygium Syndrome
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DOI：
10.1002/ajmg.a.33338
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发表时间：
2010-09-01
影响因子：
2
通讯作者：
Yoshiura, Koh-ichiro
中科院分区：
文献类型：
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作者：
Matsuzawa, Noriko;Kondo, Shinji;Yoshiura, Koh-ichiro
干扰素调节因子6基因突变（1121：6）可引起腘翼状胬肉综合征（PPS）或货车德沃德综合征（VWS），即等位基因常染色体显性口面裂。为了进一步研究PPS中的IRF 6突变谱，我们对来自两个不相关的日本PPS家族的患者进行了突变分析，并确定了IRF 6的突变：c.251G>T（R84 L）和c.1271C>T（S424 L）。我们还发现了R84 L，它与以前关于R84突变的报道一起，提供了另一条证据，表明这两种综合征可能是在修饰基因的影响下由相同的突变引起的。这支持了IRF 6的DNA结合结构域中的R84残基是PPS的突变热点的想法。另一个家族中S424 L蛋白的荧光素酶测定表明，突变使IRF 6转录活性显著降低至野生型的6%。这一发现表明IRF 6的C-末端区域可能在磷酸化或蛋白质相互作用中具有重要功能。据我们所知，这是首次在日本PPS患者中观察到突变的报告。(C)2010 Wiley-Liss，Inc.
Mutations in the interferon regulatory factor 6 gene (1121:6) 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 wildtype. 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. (C) 2010 Wiley-Liss, Inc.