Clinical, Cellular, and Molecular Investigation Into Oculocutaneous Albinism

Plain-language 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.

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