301 The Spectrum of PLEC Sequence Variants and Related Plectinopathies Including Novel Association with Epidermolysis Bullosa Pruriginosa

Plectin, a cytoskeletal linker and intermediate filament protein ubiquitously expressed in many cell types, is encoded by PLEC. Plectin consists of three main domains that determine its functionality: the N-terminal domain, rod C-terminal domain. Molecular defects PLEC correlating with functional aspects lead to group rare heritable disorders, plectinopathies. These multisystem disorders include an autosomal dominant form epidermolysis bullosa simplex (EBS-Ogna), limb girdle muscular dystrophy (LGMD), recessive (EBS), which may associate (EBS–MD), pyloric atresia (EBS–PA), and/or congenital myasthenic syndrome (EBS-MyS). In this study, genotyping over 800 Iranian patients gene-targeted sequencing panel or whole-exome identified 15 disease-causing variants. Analysis clinical spectrum plectinopathies our cohort literature indicated relationship between variant locations phenotypic manifestations. Most EBS-MD are found have at least one central domain plectin whereas EBS, EBS-PA, typically present variants outside these domains. addition, novel association homozygous nonsense was observed patient EB pruriginosa, MD, MyS. This study integrated seven previously published data totaling 115 provide most complete overview pathogenic related disorders.