Genetic analyses of Chinese patients with digenic oculocutaneous albinism

Background Oculocutaneous albinism (OCA) is a heterogeneous and autosomal recessive disorder in all populations worldwide. The mutational spectra of OCA are population-specific. Some OCA patients carry mutations from different OCA genes. In this study, we investigated the frequency of digenic mutations in Chinese OCA patients. Methods Genomic DNAs were extracted from the blood samples of 184 clinically diagnosed OCA patients and 120 unaffected subjects. The amplified DNA segments of the exons and exon-intron boundaries were screened for mutations of TYR, OCA2, TYRP1, SLC45A2, and HPS1 by direct sequencing. To exclude the previously unidentified alleles from polymorphisms, samples from 120 unaffected controls were sequenced for the same regions of variations. Results In all 184 patients, 134 had two pathologic mutations on one locus. Eleven cases had no apparent pathologic mutations in any of the genes studied. Among the remaining 39 patients who had only one pathologic mutation, five patients (2.7% in total) were found to carry the mutational alleles on a second locus in TYR, OCA2 or SLC45A2. Of the five digenic OCA patients, four patients were clinically diagnosed as OCA2 and one patient as OCA1. A previous unidentified allele p.G188D in SLC45A2 was identified, which was not present in the 120 unaffected controls. Conclusions The identification of the digenic OCA patients suggests the synergistic roles among TYR, OCA2 and SLC45A2 during melanin biosynthesis, which may cause OCA under digenic mutations. This information will be useful for gene diagnosis and genetic counseling of OCA in China. Chin Med J 2013;126 (2): 226-230