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"

This record contains the raw data (Exome sequencing) related to article "In-depth genetic and molecular characterization of DIAPH2 as a novel candidate gene for hearing loss" <strong>ABSTRACT </strong> 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 <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. <em>In-vitro</em> studies showed a possible functional impairment of the mutant DIAPH2 protein upon RhoA-dependent activation. Finally, <em>Diaph2</em> 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 <em>DIAPH2</em> may play a role in the inner ear; further studies are however needed to clarify the contribution of <em>DIAPH2</em> to deafness.