U01EY032403

Micropthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children (MAGIC) Study - 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); micropthalmia (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. Results from this study will inform genetic testing, counseling, treatment, and disease surveillance strategies for these individuals with MAC.

Emory University

1) TO SUPPORT EYE AND VISION RESEARCH PROJECTS THAT ADDRESS THE LEADING CAUSES OF BLINDNESS AND IMPAIRED VISION IN THE U.S. THESE INCLUDE RETINAL DISEASES, CORNEAL DISEASES, CATARACT, GLAUCOMA AND OPTIC NEUROPATHIES, STRABISMUS, AMBLYOPIA, AND LOW VISION AND BLINDNESS REHABILITATION. 2) TO INCREASE UNDERSTANDING OF THE NORMAL DEVELOPMENT AND FUNCTION OF THE VISUAL SYSTEM IN ORDER TO BETTER PREVENT, DIAGNOSE, AND TREAT SIGHT-THREATENING CONDITIONS, AND, TO ENHANCE THE REHABILITATION, TRAINING, AND QUALITY OF LIFE OF INDIVIDUALS WHO ARE PARTIALLY-SIGHTED OR BLIND. 3) TO SUPPORT A BROAD PROGRAM OF BASIC VISION RESEARCH THROUGH GRANTS AND COOPERATIVE AGREEMENTS, TO ENCOURAGE HIGH QUALITY CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS, OTHER EPIDEMIOLOGICAL STUDIES, AND HEALTH SERVICES RESEARCH, TO ENCOURAGE RESEARCH TRAINING AND CAREER DEVELOPMENT IN THE SCIENCES RELATED TO VISION, AND TO SPONSOR SCIENTIFIC WORKSHOPS IN HIGH PRIORITY RESEARCH AREAS TO ENCOURAGE EXCHANGE OF INFORMATION AMONG SCIENTISTS. 4) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENCOURAGE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.867 - Vision Research

National Eye Institute (NEI) [HHS - NIH]

Atlanta, Georgia 303221014 United States

Single Zip Code

Change of Recipient Organization (Type 7 Parent Clinical Trial Optional) (PA-24-254)

Amendment Since initial award the total obligations have increased 393% from $769,911 to $3,797,607.