Genetic heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB variants detected among hearing impaired families in Morocco

Abstract

Deafness has a very variable disease. It may occur as a result of external auditory canal involvement or a de ciency in the sound conduction mechanism (transmission deafness) or impairment of the cochlear, cochlear nerve or central auditory perception. Genetics is the most common cause, as approximately 70% of hearing disorders are of hereditary origin. 1/3 of hereditary deafness is syndromic (associated with other symptoms) and 2/3 are non-syndromic (isolated deafness). At this date, 173 loci of deafness gene have been reported in the literature (69 DFNA, 94 DFNB, 6 X-linked DFN, 2 DFNM, 1 DFNY and 1 AUNA1). For syndromic deafness, approximately 400 syndromes associated with hearing disorders are already described.Thus, the determination of causal mutations is a valuable aid for accurate and early diagnosis. This makes it possible to better guide the management since forms of deafness respond better to the cochlear implant than others. The correct diagnosis also gives an idea of the evolutionary pro le of deafness and whether it is a syndromic deafness requiring special surveillance. In this study, we have examined the genetic causes of sensorineural hearing loss in Moroccan patients through whole exome sequencing (WES) to identify candidate genes for six severely deaf Moroccan families. The results revealed four genetic variants in the genes GJB2, COL4A3, ATP6V1B1 and EDNRB, which are therefore common causes of syndromic and non-syndromic deafness.

Unraveling the Diversity of <i>GJB2</i> Mutations in Nonsyndromic Hearing Loss: A Comprehensive Study in the Moroccan Population

“…The results of this study revealed the presence of a rare dominant variant p.R184Q in one family. This variant was reported in the literature in several patients with autosomal dominant nonsyndromic HL, including a Moroccan family, in whom it was recently identified by whole-exome sequencing [35‒38]. p.R184Q causes arginine-to-glutamine replacement at the highly conserved 184th position.…”

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

“…Heterozygous and homozygous mutations in EDNRB and ET-3 are found in patients of Waardenburg-Shah syndrome (WS-IV) that is one kind of syndromes with genetic hearing loss (GHL) ( Huang et al, 2021 ). Homozygous mutations of the EDNRB gene can be also identified in Moroccan deaf patients ( AitRaise et al, 2022 ).…”