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

被引:10
作者
Taghizadeh, Sara [1 ,2 ]
Vazehan, Raheleh [3 ]
Beheshtian, Maryam [1 ,3 ]
Sadeghinia, Farnaz [1 ]
Fattahi, Zohreh [1 ,3 ]
Mohseni, Marzieh [1 ,3 ]
Arzhangi, Sanaz [1 ]
Nafissi, Shahriar [4 ]
Kariminejad, Ariana [3 ]
Najmabadi, Hossein [1 ,3 ]
Kahrizi, Kimia [1 ]
机构
[1] Univ Social Welf & Rehabil Sci, Genet Res Ctr, Daneshjoo Blvd,Evin St, Tehran, Iran
[2] Univ Social Welf & Rehabil Sci, Student Res Comm, Tehran, Iran
[3] Kariminejad Najmabadi Pathol & Genet Ctr, Tehran, Iran
[4] Univ Tehran Med Sci, Shariati Hosp, Dept Neurol, Tehran, Iran
基金
美国国家科学基金会;
关键词
Charcot-Marie-Tooth disease; Inherited peripheral neuropathy; Whole exome sequencing; MARIE-TOOTH DISEASE; PERIPHERAL NEUROPATHY; SENSORY NEUROPATHY; PROTEIN; MUTATIONS; IDENTIFICATION; GENETICS; ROLES; MOTOR; CMT;
D O I
10.34172/aim.2020.39
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:426 / 433
页数:8
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