Molecular Diagnosis of Hereditary Neuropathies by Whole Exome Sequencing and Expanding the Phenotype Spectrum
| Autor: | Raheleh Vazehan, Kimia Kahrizi, Hossein Najmabadi, Farnaz Sadeghinia, Sara Taghizadeh, Shahriar Nafissi, Zohreh Fattahi, Maryam Beheshtian, Sanaz Arzhangi, Ariana Kariminejad, Marzieh Mohseni |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Adolescent Hereditary spastic paraplegia Disease Iran Biology Young Adult Charcot-Marie-Tooth Disease Exome Sequencing medicine Humans Child Clinical phenotype Gene Exome sequencing Genetics Hereditary neuropathies Genetic Variation Infant General Medicine Middle Aged medicine.disease Phenotype Child Preschool Mutation Spinocerebellar ataxia Female Myelin Proteins |
| Zdroj: | Archives of Iranian Medicine. 23:426-433 |
| ISSN: | 1735-3947 1029-2977 |
| DOI: | 10.34172/aim.2020.39 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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