As the most common form of ocular albinism, ocular albinism type I (OA1) is an X-linked disorder that has an estimated prevalence of about 1:50,000. We searched for mutations through the human genome sequence draft by direct sequencing on eighteen patients with OA1, both within the coding region and in a thousand base pairs upstream of its start site. Here, we have identified eight new mutations located in the coding region of the gene. Two independent mutations, both located in the most carboxyterminal protein regions, were further characterized by immunofluorescence confocal microscopy, thus showing an impairment in their subcellular distribution into the lysosomal compartment of Cos-7A cells. The mutations found can result in protein misfolding, thus underlining the importance of the structure-function relationships of the protein as a major pathogenic mechanism in ocular albinism. Seven individuals out of eighteen (38.9%) with a clinical diagnosis of ocular albinism showed mutations, thus underlining the discrepancies between the clinical phenotype features and their genotype correlations. We postulate that mutations that have not yet been identified are potentially located in non-coding conserved regions or regulatory sequences of the OA1 gene.
- GPR143 (OA1)
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