Chavanas S, Pulkkinen L, Gache Y, Smith F J, McLean W H, Uitto J, Ortonne J P, Meneguzzi G
U385 INSERM, Faculté de Médecine, Nice, France.
J Clin Invest. 1996 Nov 15;98(10):2196-200. doi: 10.1172/JCI119028.
Plectin is a widely expressed cytomatrix component involved in the attachment of the cytoskeleton to the plasma membrane. We have recently reported that the skin and muscles of three patients affected by epidermolysis bullosa simplex with muscular dystrophy (MD-EBS), a genetic disorder characterized by skin blistering associated with muscle involvement, are not reactive with antibodies specific to plectin. We demonstrated that in the skin, lack of plectin leads to failure of keratin filaments to connect to the plasma membrane via the hemidesmosomes, whereas in the muscle the deficient expression of the molecule correlates with an aberrant localization of desmin in the muscle fibers. In this study we demonstrate that in a MD-EBS kindred with two affected members, the disease results from a homozygous nonsense mutation in the plectin (PLEC1) gene leading to a premature stop codon (CGA to TGA) and decay of the aberrant plectin messenger RNA. The segregation of the mutated allele implicates the mutation in the pathology of the disorder. These results confirm the critical role of plectin in providing cell resistance to mechanical stresses both in the skin and the muscle.
网蛋白是一种广泛表达的细胞基质成分，参与细胞骨架与质膜的附着。我们最近报道，三名患有单纯性大疱性表皮松解症伴肌肉萎缩（MD - EBS）的患者的皮肤和肌肉，MD - EBS是一种以皮肤水疱伴肌肉受累为特征的遗传性疾病，对网蛋白特异性抗体无反应。我们证明，在皮肤中，网蛋白的缺乏导致角蛋白丝无法通过半桥粒连接到质膜，而在肌肉中，该分子的表达不足与结蛋白在肌纤维中的异常定位相关。在本研究中，我们证明在一个有两名受累成员的MD - EBS家族中，该疾病是由网蛋白（PLEC1）基因的纯合无义突变导致的，该突变导致过早的终止密码子（从CGA到TGA）以及异常网蛋白信使RNA的降解。突变等位基因的分离表明该突变与疾病的病理有关。这些结果证实了网蛋白在皮肤和肌肉中赋予细胞抗机械应力能力方面的关键作用。
