# Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children (MAGIC) Study

> **NIH NIH U01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $769,911

## Abstract

ABSTRACT
Congenital defects of the eye occur in approximately 5 per 10,000 live births. While there is a paucity of
epidemiologic information about these conditions, there is a growing awareness of the long-term complications
among children with these malformations. Among the more common visually threatening congenital eye
defects are anophthalmia (total absence of the globe); microphthalmia (anomalously small eye in the orbit);
and coloboma (failure of the closure of the fetal fissure). Collectively, these defects are referred to as MAC
complex and are considered part of an embryologic continuum of ocular malformations. Although MAC
accounts for approximately 12% of permanent blindness, epidemiologic studies have provided few insights into
the causes of these conditions. While genetic studies have been more fruitful, in clinical series, the known
MAC-related genes account for less than half of cases and there are no population-based estimates of the
proportion of MAC cases attributable to genetic mutations. Thus, our understanding of the genetics of MAC
remains incomplete and there are likely to be additional, as yet, unidentified MAC genes. In addition, there
have been few efforts to systematically characterize affected individuals with respect to co-occurring
phenotypes (herein termed “deep phenotyping”), which could provide insights into the underlying etiologies of
these conditions, define genotype-phenotype correlations, and ultimately inform precision medicine efforts. Our
long-term goal is to improve prevention efforts for and clinical management of MAC. The objectives of the
current study are to 1) better define the MAC phenotype and 2) characterize the role of known and newly
identified pathogenic genetic variants that confer MAC susceptibility. We will leverage the resources of the
Texas Birth Defects Registry (TBDR), which is one of the world's largest population-based birth defects
surveillance systems that has actively monitored births throughout the state since 1999. Additionally, we will
utilize the resources of the National Institutes of Health (NIH) Clinical Center to comprehensively phenotype
cases with MAC, and the National Eye Institute (NEI) Ophthalmic Genomics Laboratory to identify genetic
variants underlying MAC phenotypes. Our multidisciplinary team of epidemiologists, ophthalmologists, and
geneticists has an established track-record in MAC research and is uniquely poised to reach our objectives
through completion of the following Aims: 1) Define the phenotypic spectrum of children diagnosed with MAC
and determine the prevalence of pathogenic variants in known and suspected MAC-related genes; 2) Conduct
deep phenotyping of individuals with MAC and their first-degree relatives; and 3) Discover novel MAC-related
genes among individuals without known pathogenic variants. This study will be the first to comprehensively
characterize the genotypic and phenotypic spectrum on a population-based sample of children living with MAC...

## Key facts

- **NIH application ID:** 10157486
- **Project number:** 1U01EY032403-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Brian Patrick Brooks
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $769,911
- **Award type:** 1
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157486

## Citation

> US National Institutes of Health, RePORTER application 10157486, Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children (MAGIC) Study (1U01EY032403-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10157486. Licensed CC0.

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