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.

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.

• Albinism
• Oculocutaneous Albinism
• Foveal Hypoplasia
• Hypopigmentation
• Nystagmus

• Goding CR. Melanocytes: the new Black. Int J Biochem Cell Biol. 2007;39(2):275-9. Epub 2006 Oct 7. Review.
• 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. Epub 2003 Sep 10.
• Creel D, O'Donnell FE Jr, Witkop CJ Jr. Visual system anomalies in human ocular albinos. Science. 1978 Sep 8;201(4359):931-3.

• INCLUSION CRITERIA:

Patients will be considered to have a convincing diagnosis of OCA if they have cutaneous evidence of hypopigmentation plus:

A. Iris transillumination documented in writing or by photograph by an ophthalmologist; AND/OR

B. Evidence of characteristic axon-misrouting by visual evoked potential; AND/OR

C. Other visual deficits consistent with albinism, including nystagmus and/or foveal hypoplasia.

EXCLUSION CRITERIA:

A patient will be excluded if she/he:

A. Has been diagnosed with a known non-oculocutaneous disorder of hypopigmentation such as Hemansky-Pudlak Syndrome, Chediak-Higashi Syndrome, or Griscelli Syndrome.

B. Has been diagnosed with a known disorder of focal hypopigmentation such as Waardenburg syndrome.

C. Is too sick to travel to the NIH.

D. If an infant under one 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.