Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)

Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma ( MAC)

Background:

- Uveal coloboma is a condition where the eye does not form normally. It occurs early in the fetus s development during pregnancy. It can lead to different kinds of eye problems, including blindness. Several genes have been linked to coloboma, but the cause of most cases is hard to find. Researchers want to study the genes of people who have coloboma and genes from their close, unaffected relatives (such as parents and siblings).

Objectives:

- To study the genes associated with uveal coloboma.

Eligibility:

- Individuals at least 1 years of age who either have uveal coloboma or are an unaffected relative (such as a parent or sibling).

Design:

• Participants will have a physical exam and medical history. They will also have a full eye exam.
• Participants with uveal coloboma may have other exams, such as imaging studies and hearing assessments.
• All participants will also provide blood, cheek swab or saliva or DNA samples for genetic testing.

Study Overview

• Status: Recruiting
• Conditions: Coloboma

Detailed Description

Objective: The objectives of this study are to: 1) define ocular, systemic and other associations in a cohort of well-phenotyped participants with microphthalmia, anophthalmia and/or uveal coloboma (MAC); 2) define risk factors and microforms of MAC in relatives of affected individuals; and 3) establish a repository of DNA and/or lymphoblastoid cell lines from participants for use in laboratory investigations.

Study Population: Six hundred (600) individuals of at least one year of age with documented MAC and their relatives will be enrolled. A subset of approximately 100 participants who are eligible and interested will be referred to enroll in this study from the Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children (MAGIC Study) at Baylor College of Medicine (Baylor Protocol # H-49046).

Design: This is a natural history/genetic repository study. Six hundred (600) participants will be enrolled over fifteen years. Participants will undergo a complete age-appropriate baseline eye examination and physical examination and provide a blood, buccal cell/saliva, or DNA sample.

Outcome Measures: The tests, data and samples collected will be analyzed to better understand the genetics of MAC. In particular, ocular and systemic associations will be defined in a cohort of well-phenotyped participants with MAC, as will the risk factors and microforms of these disorders in relatives of affected individuals.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Daniel W Claus, R.N.; Phone Number: (301) 451-1621; Email: daniel.claus@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be ascertained through other pre-existing protocols, such as the NEI Ocular Natural History protocol (16-EI-0134), the NEI Screening protocol (08-EI-0102), through another similar, existing protocol or through referral from an outside clinician after a review of pertinent medical records. To increase minority enrollment, we will send a recruitment letter and flyer to ophthalmic and genetics clinics serving diverse and minority communities in the D.C. and Baltimore metropolitan areas and local clinics with whom we have ongoing relationships. A subset of approximately 100 participants who are eligible and interested will be referred to enroll in this study from the MAGIC Study at Baylor University.

Description

• INCLUSION CRITERIA:

  1. The participant must be one year of age or older.
  2. The participant must be able to cooperate with an age-appropriate eye examination or be able to provide a copy of a complete eye examination report.
  3. The participant must be able to provide a blood, buccal/saliva or DNA sample.
  4. The participant must be able to understand and sign this protocol s informed consent form OR have a legal parent/guardian/representative with the ability to do the same.

  5. The participant must either:

     1. be affected by MAC(i) OR
     2. be an asymptomatic relative of an affected individual.

     (i)Participants will be considered to be affected if they have a clear ocular phenotype related to MAC or if they are deemed affected by other clinical evaluations (e.g., the presence of a unique, systemic manifestation cosegregating with MAC, or a rare or unique kidney finding).

     EXCLUSION CRITERIA:

     Participants who are NEI employees or subordinates or co-workers of an investigator will be excluded from this study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Coloboma; Participants with Coloboma and their family members.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The tests, data, and samples collected will be analyzed to better understand the genetics of uveal coloboma.	The tests, data, and samples collected will be analyzed to better understand the genetics of uveal coloboma.	end of study

Collaborators and Investigators

• Sponsor: National Eye Institute (NEI)
• Investigators: Principal Investigator: Brian P Brooks, M.D., National Eye Institute (NEI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2013
• Primary Completion (Estimated): December 27, 2027
• Study Completion: December 27, 2027

Study Registration Dates

• First Submitted: January 26, 2013
• First Submitted That Met QC Criteria: January 26, 2013
• First Posted (Estimated): January 29, 2013

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: February 23, 2024

More Information

Terms related to this study

• Keywords: Genetics; Natural History; Repository; Advanced Retinal Disease
• Additional Relevant MeSH Terms: Eye Diseases; Congenital Abnormalities; Eye Abnormalities; Eye Diseases, Hereditary; Coloboma; Anophthalmos; Microphthalmos
• Other Study ID Numbers: 130049; 13-EI-0049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No