P.M34T Variant on GJB2 Gene Associated to Familial Deafness and Méniere Disease in an Argentinean Family

Ménière’s disease is an inner ear disorder, characterized by vestibular and cochlear dysfunction, which presents with a symptom complex of fluctuating neurosensory hearing loss, vertigo, tinnitus and a sensation of ear fullness. The frequency of familial forms is estimated in 7-15% according to several publications. In this work we present a case of familial Ménière’s disease with the GJB2 gene pathogenic variant. Five members of a family with a family history of MD were assessed by whole exome sequencing. Of the five subjects that were studied, 3 were affected and 2 were asymptomatic. By prioritizing the variants obtained in whole exome analysis of the affected subjects (I-1, II-1 y II-2), an heterozygous mutation was detected in gene GJB2 (NM_004004.5:c.101T>C). The gene for conexine 26 (GJB2, MIM 121011), encodes protein CX26, which is part of a protein family that constitutes gap junctional channels and intercellular communication shown at the level of different inner ear structures (vascular stria, spiral prominence and spiral limbus of the cochlea). The main function of the CX26 channel in the inner ear structures is that of potassium ion homeostasis necessary for the hearing physiological mechanism. The GJB2 gene pathogenic variant causes a cochleovestibular compromise that clinically manifests itself as hearing loss with vestibular compromise. In the family presented here affected subjects with clinical manifestations compatible with MD, fulfilling the current diagnostic criteria. We can state that this pathogenic variant is a candidate to be considered when evaluating patients with familiar Ménière’s disease.