Identification of non-syndromic autosomal recessive deafness causing genes in the Omani population.

Congenital deafness is a common form of hearing impairment, occurring approximately 1 in 1000 live births, and 50 percent of these cases are hereditary with a prevalence of bilateral, disabling, non-syndromic hearing loss (NSHL) of 21/1000. In recent years there has been tremendous progress on the genetic basis of deafness. Many genes involved in syndromic and non-syndromic deafness have been identified and cloned. Because of the high frequency and clinical impact, early detection of congenital hearing impairment has become an important public health problem. The main objective of this project is to identify genes for the non-syndromic autosomal recessive deafness in Omani patients by exome sequencing. Targeted DNA enrichment and massive parallel sequencing, ranging from candidate gene sets to Whole Exome Sequencing (WES), now enable the simultaneous evaluation of hundreds to thousands of genes and their variations at the individual level, proving to be the ideal test for genetically heterogeneous diseases such as NSHL. Such large-scale, rapid and increasingly cost-effective approaches limit the effort needed to carry out sequencing studies and make it possible to genetically characterize populations.The plan of investigation will involve collection of blood samples from 100 normal (non-deaf) subjects and 21 available affected families. DNA will be extracted from whole blood using relevant kits and four samples from each family will be sequenced by using Ion proton next generation sequencing (NGS). After identification of the gene involved in the deaf samples, the whole family (normal and affected individuals) will be screened for this gene to establish its frequency or carrier status. Findings on the affected individuals will be analyzed versus control samples in cases of new loci.Congenital deafness is a major health concern in Oman. The ENT department at Al-Nahdha Hospital is a tertiary referral center, and deaf children from all over the country are referred for further investigations and management. Early detection of deafness is essential for optimal rehabilitation into community. DNA-based analysis would certainly be invaluable for the early diagnosis of deafness in infants and family counseling if the gene and mutations associated with deafness are identified for the Omani patients.