Whole Exome Sequencing Identifies a Novel Pathogenic Variation [p.(Gly194Valfs*7)] in SLC45A2 in the Homozygous State in Multiple Members of a Family in Southern India Affected with Oculocutaneous Albinism.

Deleterious mutations within the SLC45A2 gene, encoding MATP, are responsible for type 4 oculocutaneous albinism. The cytogenetic location of SLC45A2 is 5p13.2 and it comprises seven exons located over around 40 kb. Its encoded protein, MATP, is 530 amino acids long and has 12 putative transmembrane domains. MATP is synthesized within the melanocytes wherein melanogenesis takes place and melanin is contained within the specialized organelles melanosomes. Previous studies have shown that when MATP expression was reduced using siRNA in MNT-1 melanoma cells, pH was lowered within melanosomes, they became poorly melanized and tyrosinase activity was also reduced within melanocytes. People affected with this type of albinism have a range of phenotypes from a complete absence of melanin to having brown hair and brown irides. Blood was collected from a family in which four members were affected with oculocutaneous albinism and showed a complete absence of melanin in skin, hair and eyes. Screening of the TYR gene using the extracted DNA showed no mutation and therefore whole exome sequencing analysis was performed. A novel deletion mutation c.579delG (p.Gly194Valfs*7) in the SLC45A2 gene, predicted to be pathogenic and to result in both frameshift and premature termination of the MATP chain, was identified. This data adds to the information pertaining to the mutation spectrum of OCA4.