Dataset raw data related to article "In-depth genetic and molecular characterization of Diaphanous Related Formin 2 (DIAPH2) and its role in the inner ear"

<p>This record contains the raw data (Exome sequencing)&nbsp;related to article &quot;In-depth genetic and molecular characterization of DIAPH2 as a novel candidate gene for hearing loss&quot;</p> <p><strong>ABSTRACT&nbsp;</strong></p> <p>Hereditary hearing loss is characterized by an extreme genetic heterogeneity. Nowadays, whole-exome sequencing represents a reasonably cost-effective approach for both mutational screening of known deafness genes and novel disease-gene identification. Here, we investigate the role of Diaphanous-related formin 2 (DIAPH2), coding for a protein involved in actin filament elongation, in nonsyndromic hearing loss. Using whole-exome sequencing, we found a predicted pathogenic missense variant at a conserved site in&nbsp;<em>DIAPH2</em>, which segregated with nonsyndromic X-linked hearing loss in an Italian family. Our immunohistochemical studies indicated that the mouse ortholog protein Diaph2 is expressed during development in the cochlea, specifically in the actin-rich stereocilia of the sensory outer hair cells.&nbsp;<em>In-vitro</em>&nbsp;studies showed a possible functional impairment of the mutant DIAPH2 protein upon RhoA-dependent activation. Finally,&nbsp;<em>Diaph2</em>&nbsp;knock-out and knock-in mice were generated by CRISPR/Cas9 technology and auditory brainstem response measurements performed at 4, 8 and 14 weeks. However, no hearing impairment was detected, possibly due to functional redundancy/compensation by other diaphanous proteins. Our findings indicate that&nbsp;<em>DIAPH2</em>&nbsp;may play a role in the inner ear; further studies are however needed to clarify the contribution of&nbsp;<em>DIAPH2</em>&nbsp;to deafness.</p> <p>&nbsp;</p>