Expanding the Clinical Phenotype of Plectin-Related Plectinopathies



Najarzadeh Torbati P¹ ; Doosti M¹ ; Sarraf P^{2, 3} ; Boostani R⁴ ; Ahangari N^{1, 5} ; Toosi MB⁶ ; Tafakhori A^{2, 3} ; Babaei M⁷ ; Abedini S¹ ; Malek H¹ ; Maskani S¹ ; Safi M¹ ; Karimiani EG¹ Show Affiliations
Source: Iranian Journal of Public Health Published:2024

Abstract

Background: Plectinopathy-associated disorders are caused by mutations in the PLECTIN (PLEC) gene encoding Plectin protein. PLEC mutations cause a spectrum of diseases defined by varying degrees of signs, mostly with epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) and plectinopathy-related disorder is limb-girdle muscular dystrophy type 2Q (LGMD2Q). Here we report three cases with EBS-MD and LGMD2Q disorders analyzed by exome sequencing followed by mutation confirmation. Methods: A complete clinical examination was done by expert specialists and clinical geneticists in Next Generation Genetic polyclinic, Mashhad, Iran (NGC, years 2020 _2021),. Genomic DNA was extracted and evalu-ated through whole-exome sequencing analysis followed by Sanger sequencing for co-segregation analysis of PLEC candidate variants. Results: We found three cases with the plectinopathy-related disease, two patients with limb-girdle muscular dystrophy type 2Q (LGMD2Q), and the other affected proband suffers from epidermolysis bullosa simplex combined with muscular dystrophy (EBS-MD) with variable zygosity mutations for PLEC. Motor development disorder and muscular dystrophy symptoms have different age onset in affected individuals. Patients with EBS demonstrated symptoms such as blistering, skin scars, neonatal-onset, and nail dystrophy. Conclusion: We report plectinopathy-associated disorders to expand clinical phenotypes in different types of PLEC-related diseases. We suppose to design more well-organized research based on comprehensive knowledge about the genetic basis of plectinopathy diseases. © 2024 Nazarzadeh Torbati et al. Published by Tehran University of Medical Sciences.