A novel pathogenic variant of NEFL responsible for deafness associated with peripheral neuropathy discovered through next-generation sequencing and review of the literature.
J Peripher Nerv Syst
; 24(1): 139-144, 2019 Mar.
Article
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| MEDLINE
| ID: mdl-30734407
ABSTRACT
Neurofilaments are neuron-specific intermediate filaments essential for the radial growth of axons during development and the maintenance of axonal diameter. Pathogenic variants of Neurofilament Light (NEFL) are associated with CMT1F, CMT2E, and CMTDIG and have been observed in less than 1% of Charcot-Marie-Tooth (CMT) cases, resulting in the reporting of 35 variants in 173 CMT patients to date. However, only six variants have been reported in 17 patients with impaired hearing. No genotype-phenotype correlations have yet been established. Here, we report an additional case a 69-year-old female, who originally presented with axonal sensory and motor neuropathy at the age of 45, associated with moderate sensorineural hearing loss, with a slight slope at high frequencies. Next-generation sequencing identified a novel pathogenic variant c.269A > G, p.(Glu90Gly). Hearing impairment is often linked to CMT due to pathogenic variants of NEFL, especially p.(Glu90Lys) and p.(Asn98Ser), and in our case p.(Glu90Gly). These pathogenic variants are all located at hot spots, in the head domain and the two ends of the rod domain of the protein.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedad de Charcot-Marie-Tooth
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Proteínas de Neurofilamentos
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Pérdida Auditiva Sensorineural
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Female
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Humans
Idioma:
En
Revista:
J Peripher Nerv Syst
Asunto de la revista:
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia