INTRODUCTION

Hearing impairment (HI) is characterized by complex genetic heterogeneity. The evolution of next generation sequencing, including targeted enrichment panels, has revolutionized HI diagnosis.

OBJECTIVES

In this study, we investigated genetic causes in 22 individuals with non- HI.

METHODS

We customized a Haloplex kit to include 30 genes known to be associated with autosomal recessive nonsyndromic HI (ARNSHI) and Usher syndrome in North Africa.

RESULTS

In accordance with the ACMG/AMP guidelines, we report 11 pathogenic variants; as follows; five novel variants including three missense (Tyr295Cys, -Phe2089Leu and -Tyr560Cys) and two nonsense Gln122Ter and Arg104Ter) mutations; two previously reported mutations Glu57Ter and -Glu475Gly), but first time identified among Tunisian families; and four other identified mutations namely Gly808AspfsX11, -Cys113Tyr and two compound heterozygous splice site variants that were previously described in Tunisia. Pathogenic variants in and genes, in patients with convincing phenotype ruling out retinitis pigmentosa, provide strong evidence supporting their association with ARNSHI. Moreover, we shed lights on the pathogenic implication of mutations in gene in auditory function providing new evidence for its association with ARNSHI. Lack of segregation of a previously identified causal mutation -Val603Phe further supports its classification as variant of unknown significance. Our study reports absence of otoacoustic emission in subjects using bilateral hearing aids for several years indicating the importance of screening genetic alteration in gene for proper management of those patients.

CONCLUSION

In conclusion, our findings do not only expand the spectrum of HI mutations in Tunisian patients, but also improve our knowledge about clinical relevance of HI causing genes and variants.