Abstract
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. 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. 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. 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.
Highlights
Hereditary neuropathies comprise two groups of disorders: the first category is characterized by inherited peripheral neuropathies (IPNs)
Material and Methods We studied 58 patients with hereditary neuropathy who were referred for molecular diagnosis to the Genetics Research Center (GRC) of University of Social Welfare and Rehabilitation Sciences (USWR) and Kariminejad - Najmabadi Pathology & Genetics Center (KNPGC) between 2011 and 2018
The investigated patients consisted of 58 unrelated cases with a spectrum of phenotypes and with a preliminary diagnosis of hereditary neuropathies, referred to GRC and KNPGC by physicians and neurologists
Summary
Hereditary neuropathies comprise two groups of disorders: the first category is characterized by inherited peripheral neuropathies (IPNs). Concurrent with technological advances in next-generation sequencing (NGS), more than 100 genes have been implicated for different types of CMT and other clinically and genetically inherited neuropathies.[3,4]. 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.
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