Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy
Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy
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DOI：
10.1093/hmg/5.10.1539
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发表时间：
1996-10-01
影响因子：
3.5
通讯作者：
Uitto, J
中科院分区：
文献类型：
--
作者：
Pulkkinen, L;Smith, FJD;Uitto, J
在大疱性表皮松解症的一种独特的常染色体隐性变种EB-MD中，终生皮肤起泡与原因不明的晚发性肌营养不良有关。对这些患者皮肤的电子显微镜观察表明，组织分离发生在半染色体内斑块的细胞内水平，其中含有Plectin，一种高分子质量的细胞骨架相关蛋白，也在肌肉的肌膜中表达。在本研究中，我们报告了两名EB-MD患者，每个患者Plectin基因PLEC1均有纯合子缺失突变，plectin基因，PLEC1，在第一个病例中，患者和她类似的妹妹有一个纯合子9个bp的缺失突变，命名为2719de19。这导致了在小鼠和人类序列之间完全保守的23个氨基酸序列中的三个氨基酸QEA的消除，第二个家族的先证者在第5866位显示了一个单核苷酸缺失，命名为5866delC，这导致了框架移位和一个提前终止密码子的翻译，从缺失位置下游16bp的下游，半桥粒中没有plectin，如与抗plectin抗体(HD-1)的阴性免疫荧光所反映的，与基底角质形成细胞的脆性有关，暗示plectin对于中间角蛋白细丝网络与半粒嵌体复合体的结合至关重要，凝集素作为一种假定的附着蛋白在肌肉中的功能也可以解释EB-MD的临床表型，包括皮肤脆性和肌肉营养不良。
In a distinct autosomal recessive variant of epidermolysis bullosa, EB-MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology, Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle, In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1, In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences, The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion, The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes, The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.