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Arch Iran Med. 2020;23(7): 426-433.
doi: 10.34172/aim.2020.39
  Abstract View: 247
  PDF Download: 203

Original Article

Molecular Diagnosis of Hereditary Neuropathies by Whole Exome Sequencing and Expanding the Phenotype Spectrum

Sara Taghizadeh 1,2 ORCID logo, Raheleh Vazehan 3, Maryam Beheshtian 1,3 ORCID logo, Farnaz Sadeghinia 1, Zohreh Fattahi 1,3, Marzieh Mohseni 1,3, Sanaz Arzhangi 1, Shahriar Nafissi 4, Ariana Kariminejad 3, Hossein Najmabadi 1,3 * ORCID logo, Kimia Kahrizi 1 * ORCID logo

1 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
2 Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
3 Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran
4 Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
*Corresponding Authors: Kimia Kahrizi, MD; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Koodakyar Alley, Daneshjoo Blvd., Evin St., Tehran, Iran. Tel: +98-21-22180138; Email: kahrizi@yahoo.com. Hossein Najmabadi, PhD; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Koodakyar Alley, Daneshjoo Blvd., Evin St., Tehran, Iran. Tel: +98-21-22180138; Email: hnajm12@yahoo.com kahrizi@yahoo.com

Abstract

Background: Inherited peripheral neuropathies (IPNs) are a group of neuropathies affecting peripheral motor and sensory neurons. Charcot-Marie-Tooth (CMT) disease is the most common disease in this group. With recent advances in next-generation sequencing (NGS) technologies, more than 100 genes have been implicated for different types of CMT and other clinically and genetically inherited neuropathies. There are also a number of genes where neuropathy is a major feature of the disease such as spinocerebellar ataxia (SCA) and hereditary spastic paraplegia (HSP). We aimed to determine the genetic causes underlying IPNs in Iranian families.

Methods: We performed whole exome sequencing (WES) for 58 PMP22 deletion-/duplication-negative unrelated Iranian patients with a spectrum of phenotypes and with a preliminary diagnosis of hereditary neuropathies.

Results: Twenty-seven (46.6%) of the cases were genetically diagnosed with pathogenic or likely pathogenic variants. In this study, we identified genetically strong variants within genes not previously linked to any established disease phenotype in five (8.6%) patients.

Conclusion: Our results highlight the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs. Moreover, functional analysis is required for novel and uncertain variants.

Keywords: Charcot-Marie-Tooth disease, Inherited peripheral neuropathy, Whole exome sequencing
Cite this article as: Taghizadeh S, Vazehan R, Beheshtian M, Sadeghinia F, Fattahi Z, Mohseni M, et al. Molecular diagnosis of hereditary neuropathies by whole exome sequencing and expanding the phenotype spectrum. Arch Iran Med. 2020;23(7):426– 433. doi: 10.34172/aim.2020.39.
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Submitted: 05 Feb 2020
Accepted: 08 Apr 2020
ePublished: 01 Jul 2020
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