Clinical, Cellular, and Molecular Investigation Into Oculocutaneous Albinism

NCT00808106 | Completed

• 2 other identifiers: 09003509-HG-0035
• Study Type: observational
• Target: 206
• Locations: 1 country
• Sites: 1

Brief Summary

Oculocutaneous albinism (OCA) is a term used to describe inherited forms of hypopigmentation associated with 1) variable levels of cutaneous hypopigmentation, ocular hypopigmentation, and visual deficits, and 2) involvement of both of the major developmental types of pigmented cells, i.e., melanocytes and retinal pigment epithelium. OCA that affects only usually-pigmented tissues is termed isolated OCA. There are currently seven albinism types (OCA-1 to OCA-7). With the exception of OCA-5, eash is associated with a specific gene and is inherited in an autosomal recessive manner OCA-5 is a proposed type of albinism associated with the chromosomal location 4q24. OCA-1 results from defects in the enzyme tyrosinase, which catalyzes the rate-limiting step in melanin synthesis. The precise functions of the remaining genes are not yet fully understood, but several may be associated with the regulation of pH in the subcellular organelle where melanin in manufactured-the melanosome. The majority of persons with OCA have two pathogenic mutations identified in a known OCA-causing gene, but a substantial minority to not. Ocular albinism (OA) is an X-linked disorder caused by mutations in the GPR143 gene. It affects the eye in a manner similar to OCA, but has minimal or no skin manifestations. In this protocol, we have four major goals:

1. 1.To clinically and comprehensively characterize OCA types 1 - 7, and OA, with respect to the degree of hypopigmentation, genetic mutations, extent of ocular involvement, and longitudinal variation.
2. 2.To use study participants cultured melanocytes to study pigment biology, variability in pigment formation related to genotype, and response to proposed treatments. Some of this work will be performed collaboratively.
3. 3.To recruit study participants with hypopigmentation not due to known albinismcausing genes.
4. 4.To evaluate methods of quantifying eye pigmentation, skin pigmentation and other clinical parameters that may be usable as outcome measures in future treatment studies.

Conditions

Oculocutaneous Albinism

Keywords

Oculocutaneous Albinism

Outcome Measures

Primary Outcomes (4)

• A

  Collect data to refine existing knowledge about the range, course and severity of the visual, cutaneous, auditory and other potentialmanifestations of the various forms of OCA and of OA

  Ongiong

• B

  Conduct laboratory studies on patients cultured melanocytes and other biologic specimens to further understand the cell biology ofpigment formation relative to genetic mutation

  Ongoing

• C

  Pursue the discovery of novel molecular defects in patients who have albinism caused by mutations in pigmentation-related genes that have not yet been proven to be associated with human pigmentation disorders

  Ongoing

• D

  Search for and evaluate methods of quantifying eye pigmentation, skin pigmentation and other clinical parameters that may be usable as outcome measures in future treatment studies

  Ongoing

Study Arms (1)

Albinism

Patients with albinism

Eligibility Criteria

• Age: 1 Year - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with albinism

You may qualify if:

• Patients will be screened by requesting copies of the following materials at the time they contact the program:
• An indication of ethnic background by the potential participant, which may be unknown .
• Photographs of the potential participant that give an indication of skin complexion/pigmentation and undyed hair color (if available).
• Ophthalmology or other visual specialist records documenting visual exam characteristics, potentially including iris transillumination, visual evoked potential and or characteristic eye findings (if available).
• Genetic testing results (if available).

You may not qualify if:

• Significant evidence that the potential participant has either OCA1A or OCA2 with a typical presentation, AND has an ethnic background that is wellrepresented in the current study (proportion in study exceeding the proportion in the United States population).
• OCA2 cases in the current study population; and 2) that, despite this, persons with ethnicities that are underrepresented in the study may inform our understanding of populationlevel molecular patterns in OCA1A/ OCA2 and cultural implications of albinism.
• Persons who are too sick to travel safely to the NIH Clinical Center.
• A judgment by the principal investigator that clinical resources are not available to enroll additional patients at any given time.
• Persons who are currently incarcerated.
• Adults who are incompetent to consent to the protocol.
• Persons who have been diagnosed with a known nonoculocutaneous disorder of hypopigmentation such as HemanskyPudlak Syndrome, ChediakHigashi Syndrome, or Griscelli Syndrome.
• Persons who have been diagnosed with a known disorder of focal hypopigmentation such as Waardenburg syndrome.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Goding CR. Melanocytes: the new Black. Int J Biochem Cell Biol. 2007;39(2):275-9. doi: 10.1016/j.biocel.2006.10.003. Epub 2006 Oct 7.

  PMID: 17095283 BACKGROUND

• King RA, Pietsch J, Fryer JP, Savage S, Brott MJ, Russell-Eggitt I, Summers CG, Oetting WS. Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. Hum Genet. 2003 Nov;113(6):502-13. doi: 10.1007/s00439-003-0998-1. Epub 2003 Sep 10.

  PMID: 13680365 BACKGROUND

• Creel D, O'Donnell FE Jr, Witkop CJ Jr. Visual system anomalies in human ocular albinos. Science. 1978 Sep 8;201(4359):931-3. doi: 10.1126/science.684419.

  PMID: 684419 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Albinism, Oculocutaneous

Condition Hierarchy (Ancestors)

Albinism; Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• David R Adams, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2008
• First Posted: December 15, 2008
• Study Start: December 11, 2008
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: January 6, 2020

Record last verified: 2020-01

Locations

US (1)