# Unraveling the genetic architecture of cochleovestibular malformations

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $426,164

## Abstract

SUMMARY
Hearing impairment is a common and disabling sensory defect which in a subset of individuals can be due to an
abnormal cochleovestibular anatomy. Cochleovestibular (CV) and cochleovestibular nerve (CVN) anomalies can
significantly impact a child’s development and currently pose challenges in treatment and management. Little
research has been done to understand the etiology of these malformations, especially those that are non-
syndromic and severe, such as cochlear aplasia. There is a crucial need to better understand the underlying
molecular mechanisms of these conditions to aid in diagnosis, intervention and management. In addition, health
disparities exist in the molecular diagnosis and treatment of hearing impairment (HI) in Hispanics, as the
molecular etiology of HI has been scarcely studied in this ethnic group. It is imperative to study the etiology of
CV/CVN anomalies in diverse racial/ethnic populations to understand which genes/variants are a frequent cause
of this disorder in each population. Molecular diagnostics and treatment can therefore be tailored based on
population-specific information.
We hypothesize that a significant subset of severe non-syndromic CV/CVN anomalies has a genetic etiology,
which may differ between populations, and knowledge of this information will improve our understanding of inner
ear development. Our preliminary research suggests that rare genetic variants, including de novo variants, are
implicated in the development of severe CV/CVN anomalies. Our proposal leverages genomics data and
temporal bone imaging data to unravel the molecular basis of non-syndromic CV/CVN malformations. To achieve
this, we will 1) recruit and establish a large genomic database of racially/ethnically diverse families with CV/CVN
malformations which have been phenotyped in detail. 2) Next, we will determine the genetic spectrum of
underlying variation implicated in CV/CVN malformations in both Hispanic and non-Hispanic individuals. 3) Last,
using recruited and existing cohorts of individuals with CV/CVN malformations and prelingual sensorineural
hearing impairment, we will identify novel causal genes implicated in CV/CVN malformations and assess their
expression during early craniofacial and inner ear development.
We have assembled a team that has the collective expertise to achieve these aims as well as a prior track record
of productive collaboration. This work will elucidate the genetic architecture of severe non-syndromic CV/CVN
malformations diverse ethnic/racial populations and improve our basic knowledge of human inner ear
development and the mechanisms leading to abnormal development. This knowledge can then be used to
improve molecular diagnostics, guide therapeutic intervention and management, predict outcomes, and develop
novel therapeutic approaches benefiting individuals of diverse ethnicity/racial background.

## Key facts

- **NIH application ID:** 10522114
- **Project number:** 1R01DC019908-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Isabelle Veerle Suzanne Schrauwen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $426,164
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522114

## Citation

> US National Institutes of Health, RePORTER application 10522114, Unraveling the genetic architecture of cochleovestibular malformations (1R01DC019908-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10522114. Licensed CC0.

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