New Insights into the Identity of the DFNA58 Gene

Author(s)

do Nascimento, Larissa Reis ; Vieira-Silva, Gleiciele Alice ; Kitajima, Joao Paulo Fumio Whitaker ; Batissoco, Ana Carla ; Lezirovitz, Karina

• Document type: Journal article
• Source: GENES; v. 13, n. 12, p. 28-pg., 2022-12-01.

Abstract

Hearing loss is the most common sensory deficit, affecting 466 million people worldwide. The vast and diverse genes involved reflect the complexity of auditory physiology, which requires the use of animal models in order to gain a fuller understanding. Among the loci with a yet-to-be validated gene is the DFNA58, in which similar to 200 Kb genomic duplication, including three protein-coding genes (PLEK, CNRIP1, and PPP3R1's exon1), was found to segregate with autosomal dominant hearing loss. Through whole genome sequencing, the duplication was found to be in tandem and inserted in an intergenic region, without the disruption of the topological domains. Reanalysis of transcriptomes data studies (zebrafish and mouse), and RT-qPCR analysis of adult zebrafish target organs, in order to access their orthologues expression, highlighted promising results with Cnrip1a, corroborated by zebrafish in situ hybridization and immunofluorescence. Mouse data also suggested Cnrip1 as the best candidate for a relevant role in auditory physiology, and its importance in hearing seems to have remained conserved but the cell type exerting its function might have changed, from hair cells to spiral ganglion neurons. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/03433-9 - 145/5000 Use of IPS cells and animal models to elucidate the pathophysiology of post-lingual sensorineural hearing loss of genetic etiology
• Grantee: Karina Lezirovitz Mandelbaum
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/13071-6 - Identification of novel genes and functional studies in nonsyndromic deafness
• Grantee: Karina Lezirovitz Mandelbaum
• Support Opportunities: Regular Research Grants