Plectin Expression Patterns Determine Two Distinct Subtypes of Epidermolysis Bullosa Simplex
Plectin Expression Patterns Determine Two Distinct Subtypes of Epidermolysis Bullosa Simplex
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DOI：
10.1002/humu.21189
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发表时间：
2010-03-01
期刊：
影响因子：
3.9
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Natsuga, Ken;Nishie, Wataru;Shimizu, Hiroshi
Plectin是一种细胞骨架连接蛋白，具有哑铃状结构，具有长的中心杆和N-端和C-端的球状结构域。PLEC1基因突变导致大疱性表皮松解症(EB)两种不同的常染色体隐性亚型：单纯EB伴肌肉营养不良(EBS-MD)和EB单纯伴幽门闭锁(EBS-PA)。在这里，我们证明了正常人成纤维细胞表达两种不同的凝集素亚型，包括全长和无杆形式的凝集素。我们对6例EBS-MD和3例EBS-PA患者的凝集素表达模式进行了详细分析。在EBS-PA中，所有凝集素结构域的表达明显减弱或完全消失；在EBS-MD中，尽管杆状结构域的表达缺失或显著减少，但仍可检测到plectin的N-末端和C-末端结构域的表达。我们的数据表明，全长plectin亚型的丢失和无杆plectin亚型的残留表达会导致EBS-MD，而全长和无杆plectin表达的完全丧失或显著减弱是更严重的EBS-PA表型的基础。这些结果也清楚地解释了大部分EBS-MD PLEC1突变限制在编码plectin棒状域的大外显子31内，而EBS-PA PLEC1突变通常在外显子31之外。嗡嗡作响，2010年31：308-316。(C)2010年Wiley-Liss公司
Plectin is a cytoskeletal linker protein that has a dumbbell-like structure with a long central rod and N- and C-terminal globular domains. Mutations in the gene encoding plectin (PLEC1) cause two distinct autosomal recessive subtypes of epidermolysis bullosa (EB): EB simplex with muscular dystrophy (EBS-MD), and EB simplex with pyloric atresia (EBS-PA). Here, we demonstrate that normal human fibroblasts express two different plectin isoforms including full-length and rodless forms of plectin. We performed detailed analysis of plectin expression patterns in six EBS-MD and three EBS-PA patients. In EBS-PA, expression of all plectin domains was found to be markedly attenuated or completely lost; in EBS-MD, the expression of the N- and C-terminal domains of plectin remained detectable, although the expression of rod domains was absent or markedly reduced. Our data suggest that loss of the full-length plectin isoform with residual expression of the rodless plectin isoform leads to EBS-MD, and that complete loss or marked attenuation of full-length and rodless plectin expression underlies the more severe EBS-PA phenotype. These results also clearly account for the majority of EBS-MD PLEC1 mutation restriction within the large exon 31 that encodes the plectin rod domain, whereas EBS-PA PLEC1 mutations are generally outside exon 31. Hum Mutat 31:308-316, 2010. (C) 2010 Wiley-Liss, Inc.