Clinical, Cellular, and Molecular Investigation Into Oculocutaneous Albinism
Condition: Oculocutaneous Albinism
MeSH terms: Albinism; Albinism, Oculocutaneous
Study type: Observational

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. 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. 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. To recruit study participants with hypopigmentation not due to known albinismcausing
           genes.

        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.

      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.
    

Detailed description: 
      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 (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:

        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. 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. To recruit study participants with hypopigmentation not due to known albinismcausing

           genes.

        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.

      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with albinism
      
Keywords: Oculocutaneous Albinism