Analyses of FLG mutation frequency and filaggrin expression in isolated ichthyosis vulgaris (IV) and atopic dermatitis-associated IV
Analyses of FLG mutation frequency and filaggrin expression in isolated ichthyosis vulgaris (IV) and atopic dermatitis-associated IV
复制标题
DOI：
10.1111/bjd.12206
复制
发表时间：
2013-06-01
影响因子：
10.3
通讯作者：
Yao, Z.
中科院分区：
文献类型：
--
作者：
Li, M.;Cheng, R.;Yao, Z.
背景寻常性鱼鳞病（IV; OMIM 146700）是一种非常常见的遗传性皮肤病。聚丝蛋白基因（FLG）的功能缺失突变已被确定为IV的原因。在先前的研究中，我们发现与特应性皮炎（AD）相关的IV中FLG无效突变的百分比低于与AD无关的IV（孤立IV）。我们推测AD患者的某些IV临床表现不是由FLG突变引起的。目的为了阐明这一问题，我们收集了21个IV家系，33例散发性孤立性IV患者和116例AD相关IV患者，分析孤立性IV和AD相关IV中FLG突变频率和聚丝蛋白表达。方法采用重叠聚合酶链反应（PCR）策略对所有患者的FLG基因进行全面测序。我们还研究了皮肤中前聚丝蛋白/聚丝蛋白表达的免疫组织化学，并使用实时PCR测量了7名患者的mRNA表达，包括1名携带c.3321delA突变的IV患者，2名携带c.3321delA和c.6834del5突变的AD相关IV患者，结果FLG基因突变率在孤立性IV和AD相关IV患者中分别为74%和43%，分别免疫组化染色显示，所有患者表皮中的聚丝蛋白原/聚丝蛋白肽均显著减少。所有患者无论是AD或IV显示较低的FLG mRNA的表达与normalcontrol.Conclusions这些结果表明，FLG基因突变以外的因素可以下调profilaggrin/filaggrin的表达，导致鱼鳞病表型的背景下，AD。
Background Ichthyosis vulgaris (IV; OMIM 146700) is a very common inherited skin disorder. Loss-of-function mutations in the filaggrin gene (FLG) have been identified as the cause of IV. In a previous study, we found that the percentage of FLG null mutations was lower in IV associated with atopic dermatitis (AD) than in IV not associated with AD (isolated IV). We speculated that some clinical manifestations of IV in patients with AD are not induced by FLG mutations.Objectives In order to clarify this issue, we collected 21 IV pedigrees, 33 patients with sporadic isolated IV and 116 patients with AD-associated IV to analyse FLG mutation frequency and filaggrin expression in isolated IV and AD-associated IV.Methods A comprehensive sequencing of the FLG gene in all patients was performed using an overlapping polymerase chain reaction (PCR) strategy. We also studied the immunohistochemistry of profilaggrin/filaggrin protein expression in the skin and measured the mRNA expression using real-time PCR in seven patients, including one patient with IV harbouring the mutation c.3321delA, two patients with AD-associated IV harbouring c.3321delA and c.6834del5, and four patients with AD-associated IV without FLG mutations.Results The percentage of mutations in the FLG gene was 74% and 43% in patients with isolated IV and patients with AD-associated IV, respectively. Immunohistochemical staining revealed that profilaggrin/filaggrin peptides were remarkably reduced in the epidermis of all the patients. All the patients with either AD or IV showed lower FLG mRNA expression compared with the normal control.Conclusions These results indicate that factors other than FLG gene mutations can downregulate profilaggrin/filaggrin expression, leading to the ichthyosiform phenotype in the context of AD.