# Identification of Autosomal Recessive Nonsyndromic Hearing Impairment Genes

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $635,583

## Abstract

PROJECT SUMMARY/ABSTRACT
 Hearing impairment (HI) is the most common sensory deficit in the world. Congenital HI occurs in 1-2 per
1000 newborns. Understanding the mechanism of hearing will greatly aid in the development of treatment
strategies for HI. Additionally, identification of new HI genes and pathogenic variants is highly beneficial for
genetic screening so that HI can be diagnosed early, and intervention can occur to maximize the child’s
cognitive, social-emotional, speech and language development. The first step is to identify genes involved in
the etiology of nonsyndromic (NS) HI. Although 73 genes have been identified for autosomal recessive (AR)
NSHI, the vast majority of NSHI genes have yet to be uncovered. The extreme genetic heterogeneity of NSHI
is due to the complex inner ear architecture. Identification of genes involved in HI is the first step in improving
knowledge of the auditory process, which in turn will aid in the development of diagnostic modalities and
therapeutic interventions. Annually we will ascertain ~110 ARNSHI families with at least two members
affected with severe to profound bilateral sensorineural ARNSHI from Hungary (Magyar and Romani), Nigeria,
and Pakistan. DNA samples from hearing-impaired family members will be screened for genes/variants that
are common causes of ARNSHI within their respective population. There will be ~92 families to identify new
ARNSHI genes through next-generation sequencing and data analysis that uses information on variant
frequency, deleterious status, and conservation. Information clinical etiology, animal models, and inner ear
expression will also be used. Candidate variants will be validated and tested for segregation with ARNSHI
status within the pedigrees. Once a putative causal variant is identified we will screen our in-house collection
of ARNSHI exome data, use GeneMatcher, and contact our long-term collaborators to find additional ARNSHI
families that segregate potentially causal variants within the same gene. For ~20 newly identified ARNSHI
genes, expression and functional studies will also be performed using zebrafish and mice models to ensure
gene pathogenicity as well as to elucidate a better understanding of the role the genes play in the etiology of
HI. Due to the trans-Atlantic slave trade the majority of African Americans have west African ancestry;
therefore, the study of Nigerian families will impact our understanding of the etiology of HI and improve
diagnostics and treatment in this minority population. Families from Pakistan and Hungary (Magyar and
Romani) should yield new ARNSHI gene that also have public health importance in other populations.

## Key facts

- **NIH application ID:** 10809596
- **Project number:** 5R01DC003594-22
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** SUZANNE M LEAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,583
- **Award type:** 5
- **Project period:** 1998-08-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809596

## Citation

> US National Institutes of Health, RePORTER application 10809596, Identification of Autosomal Recessive Nonsyndromic Hearing Impairment Genes (5R01DC003594-22). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10809596. Licensed CC0.

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