Mutational Spectrum and Clinical Symptoms of Iranian Patients with Charcot-Marie-Tooth Disease: A Study of 23 Patients

MohammadKazem  Bakhshandeh; Asghar Ghorbani

doi:10.18502/jimc.v6i3.12853

MohammadKazem Bakhshandeh Hakim Children Hospital, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
Asghar Ghorbani Baharloo Hospital, Department of Pediatrics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/jimc.v6i3.12853

Keywords: Charcot-Marie-Tooth disease, Gene, Genetic neuropathy, Mutation spectrum, Next generation sequencing, Rare disorder

Abstract

Background: More than 80 genes are involved in the pathogenesis of the most common single gene peripheral neuropathies denoted as Charcot-Marie-Tooth (CMT). Only a few studies have investigated the pathological molecular mechanisms of Iranian patients affected with CMT. The aim of this study is to identify the clinical manifestation, mutational spectrum and phenotypic correlation of a cohort of patients with Charcot-Marie-Tooth disease (CMT) in Iran.

Methods: We conducted a comprehensive gene panel sequencing consisting of 80 genes in a cohort of 23 patients with CMT referred between January 2015 and March 2021. The recruited samples indicated almost an equal distribution of demyelinating and axonal types of CMT, with practically no difference between AD or AR patterns of inheritance.

Results: Four novel mutations, including c.271C>T in LITAF and c.205+1delG in NDRG1, c.2455A>C in KIF1B and c.1728A>G in FIGF were detected in four patients affected with demyelinating CMT types (CMT1C and CMT4D), and characterized phenotypically.

Conclusion: Our promising results unravel the complicated genetic architecture of Iranian CMT patients and help physicians and researchers achieve earlier diagnosis, better clinical management and recognizing high risk families. Further large-scale studies are needed to improve our understanding of CMT complex genetic architecture