Abolfazl Yari - Department of Medical Genetics, Kerman University of Medical Sciences, Kerman, Iran.Student Research committee, Kerman University of Medical Sciences, Kerman, Iran
Nasrollah Saleh-Gohari - Department of Medical Genetics, Kerman University of Medical Sciences, Kerman, Iran.Medical Genetic Laboratory, Samen Alhojaj Charity Center, Kerman, Iran
Milad Babasalari - Department of Medical Genetics, Kerman University of Medical Sciences, Kerman, Iran

Background: The hereditary loss of hearing is the most common sensory defect. This disorder is genetically heterogeneous. In recent years, efforts have been made to identify genetic variants associated with this disorder. Now, with the advent of next-generation sequencing (NGS) technology, provides a quick and low-cost approach to the genetic diagnosis of hearing impairments. Here, we use NGS to examine all of 127 known deaf-related genes in 12 Iranian families.Methods: In this study, we examined 12 Iranian families with hereditary loss of hearing. Mutation screening was performed in 127 known deaf-related genes using NGS. Finally, the identified variants were analyzed by SIFT and PolyPhen-2 to predict the effect of variants on protein function.Results: By Using this approach, we were able to identify the causative genes in 7 of 12 families. The pathogenic role of these variants has already been reported. In addition, 7 novel variants were specifically identified in 6 deaf-related genes. These variants are in the genes ADGRV1-c.12786C> G, GIPC3-c.265-266 ins AG and USH1C-c.1659T> A in heterozygous state and in LOXHD1-c.6463C> T, OTOF-Ex2-Ex47Dup, ALMS1-c.8665_8669delCAAAG and ALMS1-c.9457A> T were homozygous. Direct sequencing co-confirmed the presence of these novel variants in patients. Analysis of these variants showed that GIPC3-c.265-266insAG and ALMS1-c.8665_8669delCAAAG are likely pathogenic.Conclusions: In this study, we successfully used NGS technology to screen mutations in the deaf-related genes. Based on our findings, 7 novel variants were found in the deaf-related genes for the first time in Iranian population. These rare hereditary variants should be considered in genetic diagnosis and counseling.

Hearing loss, Deafness, Novel variants, deaf-related genes, Next generation sequencing (NGS)