Investigation of genes responsible for non-syndromic autosomal recessive hearing loss with next generation sequencing approach

Hearing loss is one of the most common sensory disorders that can affect all age groups. Congenital hearing loss is seen in 1 in 1000 births. More than 50% of hearing loss is due to genetic factors, while the rest is due to environmental factors. Approximately 70% of the hearing loss caused by genetic factors is non-syndromic hearing loss. Approximately 70-80% of non-syndromic congenital hearing loss is autosomal recessive, 20% is autosomal dominant, approximately 2% is X-linked, and less than 1% is mitochondrial inherited. Up to date, 114 loci have been identified as responsible for non-syndromic autosomal recessive hearing loss, and the gene responsible for 23 of these loci is not yet known. Similarly, 82 loci have been identified as responsible for non-syndromic autosomal dominant hearing loss, and the gene responsible for 15 of these loci is not yet known. In this thesis study, which aims to contribute to the elucidation of the genetic etiology of hearing loss, the responsible genetic etiologies were investigated in a total of five families with sensorineural hearing loss, four of which were autosomal recessive (TR-15, TR-37, TR-33, TR-59) and one of which was autosomal dominant (TR-16). In family TR-37, the previously reported c.1093C>T (p.Arg365*) variation on the GPSM2 gene, which has been associated with hearing loss, was determined as homozygous. In families TR-15 and TR-33, two new variations, c.889C>T (p.Arg297Cys) and c.1921delG (p.Ala641Profs*13), were determined as homozygous on the TBC1D24 and EPS8L2 genes, which have been previously associated with hearing loss, respectively. In families TR-59 and TR-16, the homozygous c.2554G>A (p.Ala852Thr) variation on the DLGAP2 gene and the heterozygous c.2141T>G (p.Leu714Arg) variation on the PHTF2 gene, which have not been previously associated with hearing loss, were determined as the strongest candidates for the genetic etiology in the families. In summary, within the scope of this thesis study conducted to elucidate the genetic etiology of sensorineural hearing loss in five families, a known variation was identified in one family, two new variations on known genes were identified in two families, and two strong candidate genes that may be associated with hearing loss were identified in two families. Keywords: Hearing loss, non-syndromic hearing loss, whole exome sequencing