Tyrosinase acts as the critical enzyme in the synthesis of melanin in melanocytes. Mutation in this gene in oculocutaneous albinism type 1 produces proteins with minimal to no activity, corresponding to the OCA1B and OCA1A phenotypes, respectively. Individuals with OCA1B have light skin, hair, and eye coloring at birth but develop some pigment during their lifetimes, while the coloring of those with OCA1A does not darken with age.
The gene product of OCA2 is a protein found in the membrane of melanosomes. Its function is unknown, but it may play a role in maintaining the structure or pH of this environment. Murine models with mutations in this gene had significantly decreased melanin production compared with normal controls.
Mutations in the genes MATP (OCA4) and TYRP1 (tyrosinase-related protein) are associated with less common types of oculocutaneous albinism. The increased risk of SCC of the skin in people with these mutations has not been quantified. It is generally assumed to be similar to other types of albinism.
Other albinism syndromes
A subgroup of albinism includes people who exhibit a triad of albinism, prolonged bleeding time, and deposition of a ceroid substance in organs such as the lungs and gastrointestinal tract. This syndrome, known as Hermansky-Pudlak syndrome, is inherited in an autosomal recessive manner but may have a pseudodominant inheritance in Puerto Rican families, owing to the high prevalence in this population. The underlying cause is believed to be a defect in melanosome and lysosome transport. A number of mutations at disparate loci have been associated with this syndrome, including HPS1, HPS3, HPS4, HPS5, HPS6, HPS7 (DTNBP1), HPS8 (BLOC1S3), and HPS9 (PLDN).[80,81,82,83,84,85,86,87] Pigmentation characteristics can vary significantly in this disorder, particularly among those with HPS1 mutations, and patients report darkening of the skin and hair as they age. In a small cohort of individuals with HPS1 mutations, 3 out of 40 developed cutaneous SCCs, and an additional 3 had BCCs. Hermansky-Pudlak syndrome type 2, which includes increased susceptibility to infection resulting from congenital neutropenia, has been attributed to defects in AP3B1.