GNAI3 sequencing

Ocular albinism type 1 (OA) caused by mutations in the OA1 gene, also called GPR143, encodes a G-protein coupled receptor, OA1, localized in melanosomal membranes of the retinal pigment epithelium (RPE). This disorder is characterized histologically by the presence of RPE macro-melanosomes and abnormal decussation of the retinal axons at the brain's optic chiasm. We demonstrated previously in mice that Oa1 specifically activates Gai3. This G-protein also signals in the Oa1 transduction pathway that regulates melanosomal biogenesis. The objective of this study was to screen the human ortholog of the mouse Gai3 gene, GNAI3, in peripheral blood samples from 26 patients who have all clinical characteristics of OA but in whom a specific mutation in the OA1 gene had not been found and in 6 normal control individuals. The Agilent HaloPlex Target Enrichment System and next-generation sequencing (NGS) on the Illumina MiSeq platform captured all exons, introns, and UTRs of the GNAI3 gene. Identified variants were corroborated with Sanger sequencing.