In silico analysis of a novel causative mutation in Cadherin23 gene identified in an Omani family with hearing loss

Abstract

Background: Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every 500 newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. It is found to be expressed in the stereocilia of hair cells and in the retina photoreceptor cells. Defective CDH23 have been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12) deafness. The purpose of this study was to identify causative mutations in an Omani family diagnosed with severe-profound sensorineural hearing loss by whole exome sequencing technique and analyzing the detected variant in silico for pathogenicity using several in silico mutation prediction software. Results: A novel homozygous missense variant, c.A7436C (p. D2479A), in exon 53 of CDH23 was detected in the family while the control samples were all negative for the detected variant. In silico mutation prediction analysis showed the novel substituted D2479A to be deleterious and protein destabilizing mutation at a conserved site on CDH23 protein. Conclusion:In silico mutation prediction analysis might be used as a useful molecular diagnostic tool benefiting both genetic counseling and mutation verification. The aspartic acid 2479 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

Review and research gap identification in genetics causes of syndromic and nonsyndromic hearing loss in Saudi Arabia

“…This was reported previously in other NSHL patients from the USA and Japanese populations (Schultz et al, 2011;Wagatsuma et al, 2007). Two different homozygous variants (p.Pro2205Leu; p.Asp2479Ala) were identified in three Qatari and two Omani NSHL families, respectively (Al-Kindi et al, 2020;Alkowari et al, 2017). These were private variants for this type of cohort that arise probably due to a founder effect (Al Mutery et al, 2022).…”