Genes involved in oculocutaneous and ocular albinism: their role, molecular analysis and diagnostic relapses
Dr. Lucia Mauri
Albinism is a rare condition characterized by an absence or a reduction in the melanin biosynthesis associated to hypopigmentation with general and specific ocular changes, such as reduced visual acuity, nystagmus, iris translucency, foveal hypoplasia and hypopigmented fundus derived from the reduction of pigment during the development of the eye. The average incidence on a global scale is 1:20.000.
This pathology includes different pathologies due to defects of different "pathways" of the melanin biosynthesis. The albino phenotype is also present in some syndromes such as the Hermansky-Pudlak syndrome, whose clinical manifestation in the first years of life is comparable to that of the oculocutaneous disease. The oculocutaneous albinism (OCA) is an hereditary autosomal recessive disease. At this moment four principal genes have been identified responsible for the different types of OCA (OCA1-4).
OCA type 1 (OCA1) is the predominant form of albinism in the world. It's caused by alterations in the gene TYR (tyrosinase enzyme), located on chromosome 11q14.2. The OCA2 form has been extensively studied in the U.S. and among African-Americans. In some parts of South Africa the affected are 1:3.900. This form of albinism is associated with defects of the P gene, located in the chromosome region 15q11.2-q12.
OCA3, sometimes referred to as type Rufous (ROCA), shows a higher prevalence in African populations, while is rare, and / or little studied in the Caucasian and Asian population. This form is caused by mutations in the gene TYRP1 (Tyrosine - related protein 1), located on the chromosome 9p23.
Mutations in the SLC45A2 gene (or MATP gene), mapped in the chromosome 5p13.3, cause the OCA4 form. Its product is a protein associated with a membrane transporter and has been most studied in Japanese patients.
The Ocular Albinism type 1 (OA1 ocular albinism or Nettleship-Falls) is the most common form of Albinism just Ocular, with a prevalence of approximately 1:60,000. This type of albinism is characterized by X-linked segregation and therefore affects only males. The OA1 is caused by mutations in the gene GPR143, located on chromosome Xp22.3. Defects in this gene cause the formation of giant melanosomes (macromelanosomes) in the retinal pigment epithelium on the cells.