Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene
Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene
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DOI：
10.1136/jmg.2005.034157
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发表时间：
2006-03-01
影响因子：
4
通讯作者：
Urban, Z
中科院分区：
文献类型：
--
作者：
Szabo, Z;Crepeau, MW;Urban, Z
背景：拉克萨是一种获得性或遗传性疾病，其特征是皮肤多余、下垂和缺乏弹性。常染色体显性遗传性皮肤松弛拉克萨是一种良性疾病，全身受累较少。目的：报道一个常染色体显性遗传性皮肤松弛拉克萨家系和一个散发性皮肤松弛拉克萨的年轻女孩，两者均具有主动脉瘤样表型的可变表达，从轻度扩张到严重动脉瘤或主动脉破裂。方法和结果：主动脉瘤标本的组织学评价表明，典型的中膜变性，缺乏弹性纤维，没有炎症或动脉粥样硬化病变的标志。电子显微镜显示细胞外弹性蛋白沉积缺乏微纤维元素。基因组扩增物直接测序检测到受影响个体的弹性蛋白基因外显子30的缺陷，但在121名正常对照中没有。通过逆转录聚合酶链反应分析皮肤拉克萨成纤维细胞，证明突变弹性蛋白mRNA形式的表达。这些基因编码多种突变的原弹性蛋白，包括C-末端截短和延伸的形式，以及缺乏组成性外显子30的分子。结论：ELN突变可能导致皮肤拉克萨患者严重的主动脉疾病。因此，定期心脏监测是必要的，在这种疾病，以避免致命的主动脉破裂。
Background: Cutis laxa is an acquired or inherited condition characterized by redundant, pendulous and inelastic skin. Autosomal dominant cutis laxa has been described as a benign disease with minor systemic involvement.Objective: To report a family with autosomal dominant cutis laxa and a young girl with sporadic cutis laxa, both with variable expression of an aortic aneurysmal phenotype ranging from mild dilatation to severe aneurysm or aortic rupture.Methods and results: Histological evaluation of aortic aneurysmal specimens indicated classical hallmarks of medial degeneration, paucity of elastic fibres, and an absence of inflammatory or atherosclerotic lesions. Electron microscopy showed extracellular elastin deposits lacking microfibrillar elements. Direct sequencing of genomic amplimers detected defects in exon 30 of the elastin gene in affected individuals, but did not in 121 normal controls. The expression of mutant elastin mRNA forms was demonstrated by reverse transcriptase polymerase chain reaction analysis of cutis laxa fibroblasts. These mRNAs coded for multiple mutant tropoelastins, including C-terminally truncated and extended forms as well as for molecules lacking the constitutive exon 30.Conclusions: ELN mutations may cause severe aortic disease in patients with cutis laxa. Thus regular cardiac monitoring is necessary in this disease to avert fatal aortic rupture.