Familial Pityriasis Rubra Pilaris Is Caused by Mutations in CARD14
Familial Pityriasis Rubra Pilaris Is Caused by Mutations in CARD14
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DOI：
10.1016/j.ajhg.2012.05.010
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发表时间：
2012-07-13
影响因子：
9.8
通讯作者：
Sprecher, Eli
中科院分区：
文献类型：
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作者：
Fuchs-Telem, Dana;Sarig, Ofer;Sprecher, Eli
红色毛癣（PRP）是一种丘疹鳞状疾病的表型相关的牛皮癣。该疾病偶尔以常染色体显性方式遗传。为了确定家族性PRP的遗传原因，我们确定了受常染色体显性PRP影响的四个不相关家族。我们最初将PRP定位于17q25.3，一个与银屑病易感位点2 （PSORS2 [MIM 602723]）重叠的区域。结合连锁分析、靶向全外显子组测序和候选基因筛选，研究人员在编码caspase募集结构域家族成员14的CARD14中发现了三种不同的杂合突变。发现CARD14在皮肤中特异性表达。CARD14是已知的核因子κ B信号的激活因子，与炎症性疾病有关。因此，在prp影响个体的皮肤中，CARD14水平升高，p65被激活。目前的数据表明，常染色体显性PRP与家族性牛皮癣等位，最近的研究表明，家族性牛皮癣也是由CARD14突变引起的。
Pityriasis rubra pilaris (PRP) is a papulosquamous disorder phenotypically related to psoriasis. The disease has been occasionally shown to be inherited in an autosomal-dominant fashion. To identify the genetic cause of familial PRP, we ascertained four unrelated families affected by autosomal-dominant PRP. We initially mapped PRP to 17q25.3, a region overlapping with psoriasis susceptibility locus 2 (PSORS2 [MIM 602723]). Using a combination of linkage analysis followed by targeted whole-exome sequencing and candidate-gene screening, we identified three different heterozygous mutations in CARD14, which encodes caspase recruitment domain family, member 14. CARD14 was found to be specifically expressed in the skin. CARD14 is a known activator of nuclear factor kappa B signaling, which has been implicated in inflammatory disorders. Accordingly, CARD14 levels were increased, and p65 was found to be activated in the skin of PRP-affected individuals. The present data demonstrate that autosomal-dominant PRP is allelic to familial psoriasis, which was recently shown to also be caused by mutations in CARD14.