| Abstract [eng] |
The Analysis of TRIOBP Gene in Lithuanian Group of Patients Affected With Non-Syndromic Hearing Loss Research object: To evaluate the importance of the TRIOBP gene pathogenic variants in etiopathogenesis of hearing impairment in Lithuanian group of patients affected with non-syndromic hearing loss. Subject relevance: Hearing loss – the most common congenital sensory impairment in the world, which is determined by genetic and the environmental factors. To date, more than 150 loci and 95 genes responsible for non-syndromic hearing loss etiology are known. The protein encoded by the TRIOBP gene is essential for formation of stereocilia's rootlets in the inner ear cochlea. Particular TRIOBP gene coding sequence variants interfere the dedevelopment of rootlets and are associated with autosomal recessive inherited hearing loss. TRIOBP gene studies in Lithuanian population have never been performed earlier, so it's important to assess significance of pathogenic variants in etiopathogenesis of hearing impairment in Lithuanian population. Research subject and methods: Were investigated 55 individuals with hereditary non-syndromic hearing loss. The object of research – patient’s DNA. TRIOBP gene coding sequence was analyzed using new generation and Sanger sequencing methods. Bioinformatic analysis was perfomed to identified TRIOBP gene coding sequence variants to determine the possible pathogenic effects of the variants to coding protein. Results and conclusions: Were sequenced TRIOBP gene exons (7, 8, 9, 16 and 17) by Sanger sequencing in Lithuanian group of 55 patients affected with non-syndromic hearing loss. About 900 TRIOBP gene sequencing reactions were perfomed and TRIOBP gene new generation and Sanger sequencing data analyzed. 24 different TRIOBP gene coding sequence variants were identified in the 7th, 8th, 9th, 14th and 19th exons. Most common variants rs8140958 (c.4129T>C, C=0.727), rs739138 (c.3899A>G, G=0.7) and rarest variants rs778331588 (c.2555A>T), rs771996937 (c.3978C>A) and rs200045032 (c.5014G>T) were determined with minor allele frequency 0.009. Based on bioinformatics tools, databases and scientific literature, 1 variant (rs200045032, c.5014G>T p.(Gly1672Ter)) was identified pathogenetically influencing the coding structure of the protein. |
