Pretibial epidermolysis bullosa: genetic linkage to COL7A1 and identification of a glycine-to-cysteine substitution in the triple-helical domain of type VII collagen.
Pretibial epidermolysis bullosa: genetic linkage to COL7A1 and identification of a glycine-to-cysteine substitution in the triple-helical domain of type VII collagen.
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胫骨前大疱性表皮松解症：与 COL7A1 的遗传连锁以及 VII 型胶原三螺旋结构域中甘氨酸到半胱氨酸取代的鉴定。
DOI：
10.1093/hmg/4.9.1579
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发表时间：
1995
影响因子：
3.5
通讯作者：
Uitto,J
中科院分区：
文献类型：
--
作者：
Christiano,AM;Lee,JY;Chen,WJ;LaForgia,S;Uitto,J
胫前大疱性表皮松解症(PEB)是一种罕见的显性营养不良性大疱性表皮松解症(DDEB)，其主要累及胫前皮肤。虽然临床上水泡似乎是局部的，但PEB患者真皮-表皮交界处的电子显微镜显示锚定纤维异常，这些异常并不局限于好发部位。此外，仅凭锚定纤维的形态不能将PEB与广义的DDEB(Cockayne-Touraine和Pasini)类型区分开来。DDEB的一般形式与染色体3p21上的II型胶原基因(COL7A1)连锁。在这项研究中，我们试图检验PEB潜在的突变也存在于COL7A1的假设。我们在一个台湾血统的五代PEB大家族中启动了COL7A1的突变分析。我们在第7867位发现了G-T颠换，导致外显子105的甘氨酸-半胱氨酸替换(G2623C)。在受影响的家系成员中，通过缺失SMA酶切位点证实了该突变，当用于连锁分析时，结合基因内的θ多态和几个侧翼标记，导致该家系在SMA=0的LOD值为Z=3.6 1。这是第一次对PEB进行遗传连锁和突变分析，并说明了DDEB的Cockayne-Touraine、Pasini和现在的胫前临床变种是等位的，是由III型胶原基因的不同甘氨酸替代突变引起的。
Pretibial epidermolysis bullosa (PEB) is a rare variant of dominant dystrophic EB (DDEB) in which recurrent blistering with scarring predominantly involves the pretibial skin. Although blistering appears to be localized clinically, electron microscopy of the dermal-epidermal junction in patients with PEB reveals anchoring fibril abnormalities that are not restricted to the predilection sites. Furthermore, PEB cannot be distinguished from the generalized (Cockayne-Touraine and Pasini) types of DDEB on the basis of anchoring fibril morphology alone. The generalized forms of DDEB have been linked to the type VII collagen gene (COL7A1) on chromosome 3p21. In this study, we sought to test the hypothesis that mutations underlying PEB also reside in COL7A1. We initiated mutational analysis in COL7A1 in a large five-generation PEB family of Taiwanese descent. We identified a G-to-T transversion at nt position 7867, which results in a glycine-to-cysteine substitution (G2623C) in exon 105. This mutation was confirmed in affected family members using the loss of a Sma\ restriction site, and when used for linkage analysis, together with an intragenicPvullpolymorphism and several flanking markers, resulted in a LOD score of Z = 3.61 at θ = 0 in this family. This is the first demonstration of genetic linkage and mutation analysis in PEB, and illustrates that the Cockayne-Touraine, Pasini, and now the pretibial clinical variants of DDEB are allelic, resulting from different glycine substitution mutations in the type VII collagen gene.