# Molecular Genetics on Non Syndromic Hearing Loss (NSHL)

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $652,246

## Abstract

ABSTRACT
Hearing loss (HL) is the most common sensory disorder affecting more than 28 million Americans and affects
15-26% of the world's population. Amongst the elderly, it ranks as the most common neurological disability,
impacting ~50% of octogenarians. Clinically significant HL is present in at least 1 per 500 infants at birth.
Recent advances in molecular technology continues to revolutionize human genetics. However, there is a
pressing need to continue identifying new human HL genes and determining 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.
Importantly, as shown in our preliminary studies, we established the comprehensive and integrated scope -
Miami Ear Institute Otogenetic Program (MEIOP) and pipelines including existence of aggregated, clinically
well-defined WES/WGS/RNAseq/non-coding causative variation and multi-omics and gene panel datasets; data
analysis platform, established the diverse Miami Otogenetic Repository (MOR) (including 60% US minorities)
that contains biological samples and clinical data on families with NSHL, a productive functional follow-up,
including model systems (cells, zebrafish); and in silico approaches of machine learning supported pathogenicity
predictions, and statistical variant burden analysis for the genetic and functional analysis of variants. In this
competitive renewal, our overarching goals are to further improve the clinical care of persons with HL and
provide a more robust foundation for therapies that target specific types of genetic HL. We will achieve these
goals by addressing current knowledge gaps as reflected in the following specific aim 1,1: To determine
causative variants in known NSHL genes and expand our minority focused populations using our well
established multi-tier genomic profiling approach. Aim 1.2: To identify novel NSHL genes using targeted
sequence capture/ whole exome/genome analysis using a customized local pipeline platform and functional
and multi-omics analysis. Aim 2: To enhance the investigation of novel disease mechanisms through
cellular/tissue assays and animal models of rare and common human HL genes/variants. Our approaches will
include functional analysis of wild type and mutant proteins in iPSCs, inner ear organoids, and animal models,
followed by characterization of their inner ear phenotypes and function. The completion of these aims will be
discoveries of novel coding and non-coding variants in genes and pathways involved in the pathophysiology of
deafness, improve clinical care for persons with hearing loss, provide a better genetic foundation for precision
medicine for the hearing impaired, and identify new targets for gene therapy for deafness in USA populations,
especially in USA minorities.

## Key facts

- **NIH application ID:** 10736532
- **Project number:** 2R01DC005575-21A1
- **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:** 2023
- **Award amount:** $652,246
- **Award type:** 2
- **Project period:** 2001-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10736532

## Citation

> US National Institutes of Health, RePORTER application 10736532, Molecular Genetics on Non Syndromic Hearing Loss (NSHL) (2R01DC005575-21A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10736532. Licensed CC0.

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