Correlation of Gene Abnormalities and Clinical Manifestations of Aniridia

Phenotype-Genotype Correlation in Aniridia

This study will examine specific gene changes in patients with aniridia, a disease in which the iris (colored part of the eye) is absent or partially absent, and will correlate the changes with clinical manifestations of the disease. In aniridia, the eye often appears to have no color, but only a larger than normal pupil. Patients may have impaired vision and cataracts, glaucoma, nystagmus (rapid, involuntary eye movements), photophobia (light sensitivity), displaced lens, underdeveloped retina, and thickened cornea. This study will focus particularly on corneal changes.

Patients 4 years old and older with aniridia may be eligible for this study. Candidates are screened with a family history and complete eye examination, including the following:

• Visual acuity testing using a vision chart.
• Eye pressure measurement.
• Fundus photography to examine the back of the eye: The pupils are dilated and special photographs of the inside of the eye are taken to evaluate the retina and measure changes that may occur over time. The camera flashes a bright light into the eye for each picture.
• Slit lamp examination: Evaluation of the front part of the eye with a special microscope called a slit lamp biomicroscope.
• Corneal thickness measurement.

Participants have blood drawn for genetic testing related to aniridia. Relevant medical information, including disease severity and complications, is obtained over time. Family members may also be requested to provide blood samples for genetic testing.

Study Overview

• Status: Completed
• Conditions: Aniridia

Detailed Description

This project, Phenotype-Genotype Correlation in aniridia, will study the specific mutations in patients with aniridia and attempt to make a phenotype-genotype correlation. Specifically, the study will determine whether specific mutations are more prevalent in aniridic patients who have a predominant involvement of the corneal epithelium. A blood sample will be collected from each individual for isolation of DNA and the PAX6 gene will be sequenced and analyzed. The principal investigator is Brian Brooks and the associated investigators are James Fielding Hejtmancik at the OMGS/OGVFB/NEI and Chi-Chao Chan, LI/NEI. Associate Investigators at collaborating institutions include Edward Holland (University of Cincinnati) and Ali Djalilian (University of Illinois, Chicago).

• Study Type: Observational
• Enrollment: 100

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Patients that meet diagnostic criteria for aniridia will be recruited from the NEI and Collaborating clinics. While diagnosis of aniridia is not expected to create significant difficulty, every attempt will be made to document the clinical status of each family member included in the study, and to document the clinical syndrome in at least one affected individual by slit lamp photography. A total of 100 subjects will be recruited for this study. There are no specific exclusion criteria other than young age (less than 4 years old) which may pose difficulty in obtaining blood.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Eye Institute (NEI)

Publications and helpful links

General Publications

• Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson L. Aniridia. A review. Surv Ophthalmol. 1984 May-Jun;28(6):621-42. doi: 10.1016/0039-6257(84)90184-x.
• Elsas FJ, Maumenee IH, Kenyon KR, Yoder F. Familial aniridia with preserved ocular function. Am J Ophthalmol. 1977 May;83(5):718-24. doi: 10.1016/0002-9394(77)90139-8.
• Mintz-Hittner HA, Ferrell RE, Lyons LA, Kretzer FL. Criteria to detect minimal expressivity within families with autosomal dominant aniridia. Am J Ophthalmol. 1992 Dec 15;114(6):700-7. doi: 10.1016/s0002-9394(14)74048-6.

Study record dates

Study Major Dates

• Study Start: December 7, 2005
• Study Completion: October 3, 2008

Study Registration Dates

• First Submitted: December 14, 2005
• First Submitted That Met QC Criteria: December 13, 2005
• First Posted (Estimate): December 14, 2005

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 30, 2017
• Last Verified: October 3, 2008

More Information

Terms related to this study

• Keywords: Aniridia; Molecular Genetics; Limbal Stem Cell Deficiency; PAX6; Keratopathy
• Additional Relevant MeSH Terms: Eye Diseases; Congenital Abnormalities; Eye Abnormalities; Genetic Diseases, Inborn; Uveal Diseases; Eye Diseases, Hereditary; Iris Diseases; Aniridia
• Other Study ID Numbers: 060044; 06-EI-0044