Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Arch Iran Med. 2020 Jul 1;23(7):426-433. doi: 10.34172/aim.2020.39.
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.
遗传性周围神经病（IPN）是一组影响周围运动和感觉神经元的神经病。Charcot-Marie-Tooth（CMT）病是该组中最常见的疾病。随着下一代测序（NGS）技术的进步，已有 100 多个基因与不同类型的 CMT 和其他临床和遗传相关的神经病有关。还有一些基因，神经病是其疾病的主要特征，如脊髓小脑共济失调（SCA）和遗传性痉挛性截瘫（HSP）。我们旨在确定伊朗家族中 IPN 的遗传原因。
我们对 58 名 PMP22 缺失/重复阴性的伊朗无关患者进行了全外显子组测序（WES），这些患者的表型范围广泛，初步诊断为遗传性神经病。
27 例（46.6%）的病例被遗传诊断为致病性或可能致病性变异。在这项研究中，我们在 5 名（8.6%）患者中发现了以前与任何已建立的疾病表型均不相关的基因中的遗传强变异。
我们的研究结果强调了在高度异质性疾病（如 IPN）中使用 WES 进行遗传诊断的优势。此外，需要对新的和不确定的变异进行功能分析。
