PDF(Pubmed)
Abstract：
Plectin, encoded by PLEC, is a cytoskeletal linker of intermediate filaments expressed in many cell types. Plectin consists of three main domains that determine its functionality: the N-terminal domain, the Rod domain, and the C-terminal domain. Molecular defects of PLEC correlating with the functional aspects lead to a group of rare heritable disorders, plectinopathies. These multisystem disorders include an autosomal dominant form of epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and an autosomal recessive form of EBS, which may associate with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS). In this study, genotyping of over 600 Iranian patients with epidermolysis bullosa by next-generation sequencing identified 15 patients with disease-causing PLEC variants. This mutation update analyzes the clinical spectrum of PLEC in our cohort and in the literature and demonstrates the relationship between PLEC genotype and phenotypic manifestations. This study has integrated our seven novel PLEC variants and phenotypic findings with previously published data totaling 116 variants to provide the most complete overview of pathogenic PLEC variants and related disorders.
摘要：
果胶,由PLEC编码，是在许多细胞类型中表达的中间丝的细胞骨架接头。果胶由决定其功能的三个主要结构域组成：N端结构域，杆域，和C末端结构域。与功能方面相关的PLEC的分子缺陷导致一组罕见的遗传性疾病，pectinopathies.这些多系统疾病包括单纯性大疱性表皮松解症（EBS-Ogna）的常染色体显性形式，肢带肌营养不良症（LGMD），先天性皮肤发育不全(ACC),和EBS的常染色体隐性形式，可能与肌营养不良（EBS-MD）有关，幽门闭锁（EBS-PA），和/或先天性肌无力综合征（EBS-MyS）。在这项研究中,通过下一代测序对600多名伊朗大疱性表皮松解症患者进行基因分型,确定了15名具有致病PLEC变异的患者.此突变更新分析了我们队列和文献中PLEC的临床谱，并证明了PLEC基因型与表型表现之间的关系。这项研究整合了我们的七个新的PLEC变体和表型发现与先前发表的总共116个变体的数据，以提供致病性PLEC变体和相关疾病的最完整概述。
