Expanding the Clinical Phenotype of PLECTIN-Related  Plectinopathies

Paria Najarzadeh  Torbati; Mohammad  Doosti; Payam  Sarraf; Reza  Boostani; Najmeh  Ahangari; Mehran Beiraghi  Toosi; Abbas  Tafakhori; Meisam  Babaei; Soheila   Abedini; Hadis  Malek; Samaneh  Maskani; Mojtaba  Safi; Ehsan Ghayoor  Karimiani

doi:10.18502/ijph.v53i5.15600

Paria Najarzadeh Torbati Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran
Mohammad Doosti Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran
Payam Sarraf Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Reza Boostani Department of Neurology, Mashhad University of Medical Sciences, Mashhad, Iran
Najmeh Ahangari Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran
Mehran Beiraghi Toosi Pediatric Neurology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
Abbas Tafakhori Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Meisam Babaei Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnourd, Iran
Soheila Abedini Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran
Hadis Malek Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran
Samaneh Maskani Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran
Mojtaba Safi Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran
Ehsan Ghayoor Karimiani Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran

DOI: https://doi.org/10.18502/ijph.v53i5.15600

Keywords: Plectinopathy; Genetics; Muscular dystrophy; Myopathy

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 evaluated 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.