# Genetics of Early Onset Retinal Diseases

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $345,120

## Abstract

The goal of this project is to better understand the molecular mechanisms of Leber congenital amaurosis (LCA),
the most common hereditary cause of visual impairment in infants and children. To accomplish this, functional
studies of CWC27, a newly identified LCA-associated disease gene that encodes a splicing factor, will be
performed using both in vitro and in vivo methods. In addition, several novel candidate genes whose mutations
cause LCA have been identified by characterizing our collection of over 1,000 unrelated LCA patient families.
We will establish mouse models for five of these newly LCA associated disease genes, and through follow up
functional studies of these models we expect to gain new insights into disease mechanisms as well as lay the
foundation for developing new diagnoses and treatment methods.
One significant gap in our current understanding of LCA is that about 1/3 of patients cannot be explained by
mutations in known retinal disease genes. To close this gap, we have collected over 1,000 unrelated LCA
patient families across the world. Screens for mutations in known LCA and other related inherited retinal
disease genes has led to the identification of causal mutations in 705 probands, leaving about 350 patient
families that remain unsolved. Patients from these families are likely due to carry mutations in novel LCA
disease genes, representing a well characterized, rich resource for identifying new genes that can cause LCA.
Indeed, whole exome sequencing of these unassigned patient families has led to the publication of four novel
disease genes. One of these genes is CWC27, for which we have established knock out and knock in mouse
models that mimic human patient phenotypes. In parallel, we plan to identify the underlying mutations in the
remaining probands using a combination of whole exome and genome sequencing, bioinformatics, and
statistics. Functional studies will be performed on five of the top candidates to elucidate the underlying
molecular mechanisms for LCA disease pathology. Our Specific Aims are to:
Specific Aim 1. Characterize the novel LCA disease gene CWC27
Specific Aim 2. Identify and perform functional studies of novel LCA disease genes
Specific Aim 3. Investigate the full spectrum of mutations contributing to LCA
Discovery and functional characterization of novel LCA genes will assist the development of new diagnostic
tools and treatments. In addition, since mutations in LCA disease genes also cause other retinal dystrophies,
functional studies of additional LCA disease genes will provide important insights into the molecular
mechanisms underlying retinal dystrophies in general.

## Key facts

- **NIH application ID:** 10155491
- **Project number:** 5R01EY018571-13
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** RUI CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,120
- **Award type:** 5
- **Project period:** 2007-12-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155491

## Citation

> US National Institutes of Health, RePORTER application 10155491, Genetics of Early Onset Retinal Diseases (5R01EY018571-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155491. Licensed CC0.

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