Molecular Diagnosis of Hereditary Neuropathies by Whole Exome Sequencing and Expanding the Phenotype Spectrum.
Arch Iran Med
; 23(7): 426-433, 2020 07 01.
Article
en En
| MEDLINE
| ID: mdl-32657593
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Variación Genética
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Enfermedad de Charcot-Marie-Tooth
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Secuenciación del Exoma
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Proteínas de la Mielina
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Child
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Child, preschool
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Female
/
Humans
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Infant
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Arch Iran Med
Año:
2020
Tipo del documento:
Article
País de afiliación:
Irán