Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris.
Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris.
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DOI：
10.1038/sj.jid.2008.2
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发表时间：
2008-07
期刊：
影响因子：
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通讯作者：
Huijia Chen;Jean C C Ho-Jean-C-C-Ho-2253898684;A. Sandilands;Yuin Chew Chan;Y. Giam;Alan T Evans;E. Lane;W. McLean
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文献类型：
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作者：
Huijia Chen;Jean C C Ho-Jean-C-C-Ho-2253898684;A. Sandilands;Yuin Chew Chan;Y. Giam;Alan T Evans;E. Lane;W. McLean
聚丝蛋白是外表皮的丰富蛋白质，其对于角质形成细胞的终末分化和形成针对水分损失和病原体/过敏原/刺激物入侵的有效屏障是必需的。最近在欧洲和日本的研究表明，聚丝蛋白基因（FLG）的无效突变是寻常鱼鳞病（IV）的根本原因，寻常鱼鳞病是一种常见的皮肤疾病，其特征是皮肤干燥、手掌超线性和毛发角化病。在制定FLG综合分析策略后，我们在新加坡华人IV患者中发现了5种独特突变和1种复发突变。突变441 delA位于聚丝蛋白原S100结构域中，而另外两个移码突变1249 insG和7945 delA分别发生在聚丝蛋白第一部分重复序列（“重复序列0”）和聚丝蛋白重复序列7中。无义突变Q2147 X和E2422 X均发现于聚丝蛋白重复序列6中，而R4307 X发现于FLG的一个较长大小的变异等位基因上，在重复序列10.2内。突变E2422 X，以前发现在一个单一的荷兰患者，被发现在一个新加坡IV患者和低频率的亚洲人群控制。我们的研究证实了新加坡人群特异性和复发性FLG突变的存在。
Filaggrin is an abundant protein of the outer epidermis that is essential for terminal differentiation of keratinocytes and formation of an effective barrier against water loss and pathogen/allergen/irritant invasion. Recent investigations in Europe and Japan have revealed null mutations in the filaggrin gene (FLG) as the underlying cause of ichthyosis vulgaris (IV), a common skin disorder characterised by dry skin, palmar hyperlinearity and keratosis pilaris. Following the development of a strategy for the comprehensive analysis ofFLG, we have identified five unique mutations and one recurrent mutation in Singaporean Chinese IV patients. Mutation 441delA is located in the profilaggrin S100 domain, whereas two additional frameshift mutations, 1249insG and 7945delA, occur in the first partial filaggrin repeat (“repeat 0”) and in filaggrin repeat 7, respectively. Both nonsense mutations Q2147X and E2422X are found in filaggrin repeat 6, whereas R4307X was found on one of the longer size variant alleles ofFLG, within duplicated repeat 10.2. Mutation E2422X, previously found in a single Dutch patient, was found in one Singaporean IV patient and at a low frequency in Asian population controls. Our study confirms the presence of population-specific as well as recurrentFLGmutations in Singapore.