MOLECULAR OUTCOMES, CLINICAL CONSEQUENCES, AND GENETIC DIAGNOSIS OF OCULOCUTANEOUS ALBINISM IN PAKISTANI POPULATION.

Abstract

Oculocutaneous Albinism (OCA) refers to a group of genetic disorders characterized by a reduction or complete lack of melanin pigmentation in the hair, skin and eyes. Melanin is the pigment produced by melanocytes that gives skin, hair and eyes their color. 1 OCA results from defects in genes involved in the biosynthesis or transport of melanin within melanocytes. To date, mutations in six different genes have been shown to underlie OCA subtypes. These genes encode enzymes and transport proteins that function at different steps of the melanin production pathway.

OCA presents with considerable inter- and intra-familial variation in pigmentation depending on the specific gene affected. 2 Based on clinical features and inheritance patterns, OCA has been classified into four main subtypes - OCA1-4. OCA1 is caused by mutations in the tyrosinase (TYR) gene and typically results in an absence of pigment production. OCA2, due to variants in the OCA2 gene, is characterized by variable hypopigmentation. 3 Mutations in TYRP1 cause OCA3 while variants in SLC24A5 underlie OCA4. In addition to hypopigmentation of skin and hair, individuals with OCA often experience ocular abnormalities such as nystagmus, photophobia and refractive errors that can cause visual impairment. 5