# Biallelic MINAR2 variant is associated with nonsyndromic severe to profound sensorineural hearing loss

## TL;DR

A genetic variant in MINAR2 causes severe hearing loss without other symptoms, confirmed in a new family through genetic sequencing.

## Contribution

This study confirms MINAR2 as a causative gene for nonsyndromic hearing loss through a new family case and genetic analysis.

## Key findings

- A homozygous nonsense variant in MINAR2 was identified in a family with nonsyndromic severe to profound hearing loss.
- The variant is predicted to cause loss of function through nonsense-mediated decay.
- This is the first independent confirmation of MINAR2-related sensorineural hearing loss.

## Abstract

MINAR2 is essential for normal hearing by regulating cholesterol localization in stereocilia in hair cells. MINAR2 knockout results in rapidly progressive sensorineural hearing loss (SNHL) in mice and zebrafish models. Recently, biallelic variants in MINAR2 have been reported to cause SNHL in four unrelated families with nonsyndromic severe to profound SNHL. Here we provide a second report of an additional family with SNHL. The index patient presented with nonsyndromic severe to profound SNHL. The family history was remarkable for a 20-year-old male sibling with nonsyndromic severe to profound SNHL. Both patients did not have any neurological involvement. Trio whole-exome sequencing of the index and his parents revealed a homozygous nonsense variant in MINAR2 (NM_001257308.2:c.319A>T; p.(Lys107*) in the index. Parents were heterozygous for the same variant. This variant introduces an early stop codon and probably results in a loss of function because of the predicted nonsense-mediated decay. Our study provides the first independent confirmation of the MINAR2-related SNHL.