Clinical, Cellular, and Molecular Investigation 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 is considered isolated if it involves only tissues that are normally pigmented. The four known types of isolated oculocutaneous albinism (OCA-1 to OCA-4) are autosomal recessive disorders associated with specific genes. OCA-1 results from defects in the enzyme tyrosinase, which catalyzes the rate-limiting step in melanin synthesis. The precise functions of the genes associated with OCA2, OCA3 and OCA4 are not known. OCA-2 is caused by mutations in the OCA2 (or P) gene. OCA-3 and OCA-4 are rare, incompletely characterized conditions caused by the tyrosine-related protein 1 gene (TYRP1) and the SLC45A2 gene, respectively. Most OCA patients have two pathogenic mutations identified in an OCA-causing gene. In this protocol, we have 4 major goals. First, we want to clinically and comprehensively characterize OCA subtypes, especially OCA-1 and OCA-2, with respect to the degree of hypopigmentation, genetic mutations, and extent of ocular involvement. Second, we plan to study patients' cultured melanocytes for variability in pigment formation related to genotype, and test treatments to increase pigmentation. Third, we expect to ascertain rare patients with hypopigmentation not due to known albinism-causing genes. Finally, we will acquire sufficient experience in the care of patients with albinism to become experts in this disorder. This expertise will be especially valuable for potential future clinical trials. We will clinically evaluate patients of all ethnicities; obtain cells, plasma and urine for future studies; perform mutation analysis on known OCA causing genes; and search for other genes responsible for OCA. Routine admissions will last 4-5 days and occur every two years.