Clinical, Cellular, and Molecular Investigation Into Oculocutaneous Albinism

January 3, 2020 updated by: National Human Genome Research Institute (NHGRI)

Clinical, Cellular, and Molecular Investigations Into Oculocutaneous Albinism

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:

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.
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.
To recruit study participants with hypopigmentation not due to known albinismcausing genes.
To evaluate methods of quantifying eye pigmentation, skin pigmentation and other clinical parameters that may be usable as outcome measures in future treatment studies.

To achieve those goals, we will perform clinical evaluations of persons with OCA and OA at the NIH Clinical Center; obtain cultured cells, plasma, serum and urine for future studies; and, perform mutation analysis on known OCA and/or OA genes and search for other genes responsible for albinism. Routine admissions will last 3 - 4 days and occur every 2 - 3 years.

Study Overview

Status

Completed

Conditions

Oculocutaneous Albinism

Detailed Description

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 (see Table 1). 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:

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.
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
To recruit study participants with hypopigmentation not due to known albinismcausing
genes.
To evaluate methods of quantifying eye pigmentation, skin pigmentation and other

clinical parameters that may be usable as outcome measures in future treatment studies.

To achieve those goals, we will perform clinical evaluations of persons with OCA and OA at

the NIH Clinical Center; obtain cultured cells, plasma, serum and urine for future studies; and,

perform mutation analysis on known OCA and/or OA genes and search for other genes

responsible for albinism. Routine admissions will last 3 - 4 days and occur every 2 - 3 years.

Study Type

Observational

Enrollment (Actual)

206

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Maryland
  - Bethesda, Maryland, United States, 20892
    - National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with albinism

Description

INCLUSION CRITERIA:

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).

EXCLUSION CRITERIA:

Exclusion from the study will be made based on one or more of the following criteria:

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).
The rationale for this exclusion is that: 1) from a biologicaland clinicalresearch perspective, we have an adequate number of OCA1A/
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 under 1 year of age. This exclusion occurs because there is no urgency for a very early evaluation. Also, the Clinical Center staff and resources are more suited for the care of older children.
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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Cohort
Time Perspectives: Prospective

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Albinism Patients with albinism

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A Time Frame: Ongiong	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 Time Frame: Ongoing	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 Time Frame: Ongoing	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 Time Frame: Ongoing	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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Human Genome Research Institute (NHGRI)

Investigators

Principal Investigator: David R Adams, M.D., National Human Genome Research Institute (NHGRI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

NIH Clinical Center Detailed Web Page

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 11, 2008

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

December 12, 2008

First Submitted That Met QC Criteria