ESTUDIO CLÍNICO Y GENÉTICO DE NEUROPATÍAS PERIFÉRICAS: WHOLE EXOME SEQUENCE (WES) Y ANALISIS BIOINFORMÁTICO.

Abstract

[ES]La neuropatía periférica (NP) hereditaria presenta gran heterogeneidad clínica y genética. La prevalencia oscila entre 3 a 6%. Clínicamente es motora, sensitiva o mixta y por su naturaleza, axonal o desmielinizante. Estas características, definen un perfil clínico que orienta a la etiología. En las polineuropatías crónicas, su origen genético suele conducir a una odisea diagnóstica. En este estudio,

partiendo de un caso clínico, se desarrolló un algoritmo clínico-genómico-bioinformático en base a Whole- Exome-Sequence(WES) familiar. Con WES se determinó la mutación de novo (R974L, proteína NMHC-IIC,

gen MYH14) como causa probable de CMT axonal, sin sordera ni ronquera, en un tiempo razonable. Así, se ha asociado este fenotipo clínico previamente no descrito, a la mutación encontrada (similar a otros, probable alteración mitocondrial). Esto apoya a WES como solución a la odisea diagnóstica, permitiendo un mejor manejo de pacientes y familiares, así como la posibilidad de plantear estudios derivados de este modelo.

[EN]Hereditary peripheral neuropathy (PN) shows great clinical and genetic heterogeneity. The prevalence ranges from 3 to 6%. Clinically it is motor, sensitive or mixed and by its nature axonal or demyelinating. These characteristics define a clinical profile that guides the etiology. In chronic polyneuropathies, their

genetic origin often leads to a diagnostic odyssey. In this study, starting from a clinical case, a clinical- genomic-bioinformatic algorithm based on Whole-Exome-Sequence (WES) of a family was developed.

With WES, the de novo mutation (R974L, NMHC-IIC protein, MYH14 gene) was determined as a probable cause of axonal CMT, without deafness or hoarseness, in a reasonable time. Thus, this previously undescribed clinical phenotype has been associated with the mutation (similar to others, probable mitochondrial alteration). This supports WES as a solution to the diagnostic odyssey, allowing better management of patients and families, as well as the possibility of proposing studies derived from this model.