# Molecular Genetics on Non Syndromic Hearing Loss (NSHL)

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $602,394

## Abstract

Abstract: Hearing loss (HL) is the most common sensory disorder affecting more than 28 million Americans. Clinically
significant HL is present in at least 1 per 500 infants at birth. Nearly 70% of HL expressed at birth has a genetic etiology.
At least 80% of nonsyndromic deafness is autosomal recessive (ARNSHL). The identification of these genes has
dramatically improved the clinical diagnosis and management of deaf and hard-of-hearing families. However, there is a
pressing need to continue identifying new human HL genes and to determine causative variants in known NSHL genes
for completing a genomic and phenotypic database. This is critical as we and others have provided direct evidence of
further genetic heterogeneity of HL with a number of genes/mutations yet to be identified: causative variants are found in
less than 4 0 % of cases and recent studies suggest that over a thousand genes are involved in deafness suggesting there are
many deafness-causative genes still remaining to be identified in both human and mouse. Identifying all of the HL genes
and causative mutation is imperative to our understanding of the biology of normal hearing and the disease
etiology/processes, provides immediate benefit to the families involved for counseling and diagnosis, and, at the molecular
level, allows for the development of novel gene-specific and even mutation-specific therapies to treat HL. The latter by using
genome editing that can have much wider use than just in the families with mutations in that gene. Importantly, as shown
in our preliminary studies, we have already collected DNA samples and phenotype data from a large international cohort
(Miami Otogenetic Repository) of families with NSHL, well established the Miami Otogenetic Clinic and pipelines for the
genetic and functional analysis of variants, excluded all known HL genes in a large cohort of multiplex families, successfully
identified many potential new candidate genes, and generated several animal models with deafness phenotype for these human
deafness genes using the CRISPR/Cas9 system and traditional targeted mutagenesis approach. In this proposal, we will
build on our previous accomplishments and preliminary data by proposing to complete the following specific aims: 1) to
determine causative variants in known NSHL genes for expanding a combined genomic and phenotypic deafness database;
2) to identify novel ARNSHL genes using targeted sequence capture/ whole exome (WES)/genome (WGS) analysis
using a customized local pipeline platform; 3) to determine functional consequences of deafness genes with in vitro and
in vivo models using innovative approaches. We will perform one of the largest and most integrated
clinical/genomic/functional studies on ARNSHL to date. This innovative study will not only increase our understanding of the
biology of hearing and deafness, but will be highly translational leading to improvements in the etiological diagnosis of
NSHL and patient care as well as pave t...

## Key facts

- **NIH application ID:** 9987591
- **Project number:** 5R01DC005575-19
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** XUE Z LIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $602,394
- **Award type:** 5
- **Project period:** 2001-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987591

## Citation

> US National Institutes of Health, RePORTER application 9987591, Molecular Genetics on Non Syndromic Hearing Loss (NSHL) (5R01DC005575-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987591. Licensed CC0.

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