文献简介

出版社:PLOS ONE

作  者:Corrado Occella, Dario Bleidl, Paolo Nozza, Samantha Mascelli, Alessandro Raso, Giorgio Gimelli, Stefania Gimelli, Elisa Tassano

编  号:

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年  份:2013   点击量:896

文献摘要

Abstract

Porokeratosis is a rare disease of epidermal keratinization characterized by the histopathological feature of the cornoid lamella, a column of tightly fitted parakeratocytic cells, whose etiology is still unclear. Porokeratosis of Mibelli is a subtype of porokeratosis presenting a single plaque or a small number of plaques of variable size located unilaterally on limbs. It frequently appears in childhood and occurs with a higher incidence in males. Cytogenetic analyses were performed in all members of the family on lesioned and uninvolved skin. An array-CGH analysis was also performed utilizing the Human Genome CGH Microarray Kit G3 400 with 5.3 KB overall median probe spacing. Gene expression was performed on skin fibroblasts. In this study, we describe a Caucasian healthy 4-year-old child and his father showing features of porokeratosis of Mibelli. Array-CGH analysis revealed an interstitial 429.5 Kb duplication of chromosome 18p11.32-p11.3 containing four genes, namely: SMCHD1, EMILIN2, LPIN2, and MYOM1 both in patient and his father. EMILIN2 resulted overexpressed on skin fibroblasts. Also other members of this family, without evident signs of porokeratosis, carried the same duplication. Among these genes, we focused our attention on elastin microfibril interfacer 2 (EMILIN2) gene. Apoptosis plays a fundamental role in maintaining epidermal homeostasis, balancing keratinocytes proliferation, and forming the stratum corneum. EMILIN2 is known to trigger the apoptosis of different cell lines negatively affecting cell survival. It is expressed in the skin. We could speculate that the duplication and overexpression of EMILIN2 cause an abnormal apoptosis of epidermal keratinocytes and alter the process of keratinization, even if other epigenetic and genetic factors could also be involved. Our results could contribute to a better understanding of the pathogenesis of porokeratosis of Mibelli.

摘要

    汗孔角化症是一种罕见的表皮角质化疾病,以组织病理学上存在角质样板层为特征,由紧紧排列的角化不全细胞组成的一个细胞柱,其病因学目前仍不清楚。汗孔角化症是汗孔角化病的一个亚型,其临床表现为位于单侧四肢的单个斑块或少数大小不一的斑块。通常在幼年期发病,在男性中发病率较高。我们对家庭所有成员的皮损处及未受累皮肤处进行了细胞遗传学分析。我们还利用整体探针间距中间值为5.3 KB人类基因组微阵列CGH试剂盒的G3 400进行微阵列比较基因组杂交(array-CGH)分析。在皮肤成纤维细胞上进行基因表达。在这项研究中,我们描述了具有汗孔角化症特征的一个4岁健康的白人小孩和他父亲。微阵列比较基因组杂交(array-CGH)分析显示患者和他父亲两者的染色体18p11.32 - p11.3上的一个间隙429.5 KB的重叠包含四个基因,即:SMCHD1EMILIN2LPIN2MYOM1EMILIN2导致了皮肤成纤维细胞过度表达。并且,这个家庭的其他成员并无汗孔角化症的明显迹象,均携带相同的副本。在这些基因中,我们的注意力集中在弹性蛋白微原纤维界面因子2(EMILIN2基因。细胞凋亡在维持表皮稳态、平衡角质细胞增殖和形成角质层中起基础性作用。我们已知EMILIN2可以触发不同细胞系的细胞凋亡,对细胞存活起消极影响。它在皮肤中表达。我们可以推测,EMILIN2的复制和过表达能够导致表皮角质形成细胞的异常凋亡并改变角化作用过程,即使可能还涉及其它的表观因素和遗传因素。我们的研究结果可能有助于更好地理解汗孔角化症的发病机制。