Molecular Genetics of Retinal Degenerations

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) ) Identifier:
First received: September 30, 2005
Last updated: December 2, 2015
Last verified: November 2015

This multinational study will investigate the inheritance of genetic retinal degeneration in families of different nationalities and ethnic backgrounds in order to identify the genes that, when altered, cause retinal degeneration. The retina is a light-sensitive membrane lining the back part of the eye. It relays vision signals to the brain, which the brain interprets into sight. When the retina degenerates, vision is altered and possibly lost. The findings of this study should help improve diagnosis and methods of treatment for these disorders. Participating institutions include: the National Institutes for Health in Bethesda, Maryland; the University of Miami in Florida; the Casey Eye Institute in Portland, Oregon; the Byrd Health Sciences Center in Morgantown, West Virginia; the University of Texas Southwestern Medical School in Dallas, Texas; the University of Tennessee Health Sciences Center in Memphis; the Prasad Eye Institute in Hyderabad, India; National Center of Excellence in Molecular Biology in Lahore, Pakistan; and the Jules Gonin Hospital in Lausanne, Switzerland.

Patients with retinitis pigmentosa and closely related diseases such as Usher syndrome, snowflake vitreoretinal dystrophy and Bietti crystalline dystrophy may be eligible for this study. Participants undergo the following tests and procedures:

  • Medical and surgical history, including family history of vision problems.
  • Examination to clarify the type of retinal degeneration.
  • Eye examination, including tests of color vision, field of vision and ability to see in the dark
  • Electroretinogram to test the function of visual cells. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small electrode (silver disk) is taped to the forehead and the eye patches are removed. The surface the eyes is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside a large dark globe that emits a series of light flashes. Then a light is turned on inside the globe and more lights flash. The contact lenses sense small electrical signals generated by the retina when the light flashes.
  • Hearing tests for patients with a personal or family history of deafness. Tests include an audiogram, ear examination and test of middle ear function. For middle ear function testing, the patient feels a little air pressure change for a moment and hears some tones. Another test requires the patient to sit quietly with electrodes on the head, forehead and earlobes.
  • Balance testing, including walking in a straight line, standing with eyes closed in the dark and other tests of coordination, and caloric testing. For the caloric testing, any ear wax in the ear canal is removed before the test begins. Then, electrodes are placed on the skin near the eyes and on the forehead. A small amount of cool (sometimes cold) or warm water is instilled into each ear canal, first one and then the other.
  • Blood sample collection for genetic testing.

Retinal Degeneration
Retinitis Pigmentosa

Study Type: Observational
Official Title: Molecular Genetics of Retinal Degenerations

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • V [ Time Frame: Ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 5000
Study Start Date: September 2005
Detailed Description:

Objective: This project, Molecular Genetics of Retinal Degenerations will study the inheritance of genetic retinal degenerations, both Mendelian and complex, in families of many nationalities and ethnic backgrounds in order to identify the genes that, when mutated, cause retinal degenerations and the pathophysiology through which they act.

Study Population: The number of subjects to be enrolled has no logical upper limit, but will be at least 250 and below 5,000 during the next 5 years. The study consists of ascertaining individuals, and especially families with multiple individuals, affected by retinal degenerations including retinitis pigmentosa (RP) and also other closely related retinal degenerations such as Usher syndrome (USH) and Bietti crystalline dystrophy (BCD).

Design: These patients and their families will undergo detailed ophthalmological examinations and, where indicated, additional non-investigational examinations to characterize their retinal degeneration and determine their affectation status. A blood sample will be collected from each individual for isolation of DNA and in some individuals for lymphoblastoid transformation to establish a renewable source of DNA. Linkage analysis, association analysis, physical mapping, and mutational screening will be carried out to identify the specific gene and the mutations in it that are associated with retinal degenerations in this family. If necessary, the gene product will be characterized biochemically.

Outcome Measures: Linkage will be determines using the lod score method and mutations in specific genes will be assessed using a combination of residue conservation, blosum score, and molecular modeling. Association will be determined using chi-square and Fisher exact tests. Biochemical, metabolic, and physiological effects will be individualized to the specific assay.


Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Patients that meet diagnostic criteria for specific retinal degenerations will be recruited from the NEI and collaborating clinics.

Subjects with the following will be recruited:

  1. Individuals or family members of individuals with Retinal degenerations, either congenital, childhood, or age related.
  2. Adults must be capable of providing their own consent.
  3. All subjects must be able to cooperate with study examination and phlebotomy.
  4. Older than 4 years of age.


  1. Diseases, infections, or trauma that mimic primary retinal degenerations.
  2. Children requiring sedation for study procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00231010

Contact: James F Hejtmancik, M.D. (301) 435-1598

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
United States, Massachusetts
Harvard Medical School Recruiting
Boston, Massachusetts, United States, 02115
United States, Ohio
Cleveland Clinic Foundation Childrens Hospital Recruiting
Cleveland, Ohio, United States, 44195
Sun Yat-Sen University Recruiting
Guangzhou, China, 510275
Aravind Eye Hospital Recruiting
Maduri, India
University of Punjab Recruiting
Lahore, Pakistan
Sponsors and Collaborators
National Eye Institute (NEI)
Principal Investigator: James F Hejtmancik, M.D. National Eye Institute (NEI)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) ) Identifier: NCT00231010     History of Changes
Other Study ID Numbers: 050143  05-EI-0143 
Study First Received: September 30, 2005
Last Updated: December 2, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Retnitis Pigmentosa
Retinal Degeneration
Retinitis Pigmentosa
Usher Syndrome
Bietti Crystalline Dystrophy

Additional relevant MeSH terms:
Retinal Degeneration
Retinitis Pigmentosa
Eye Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Retinal Diseases
Retinal Dystrophies processed this record on May 23, 2016