作者: | Ai-Hua Wei,Dong-Jie Zang,Zhe Zhang,Xuan-Zhu Liu,Xin He,Lin Yang,Yi Wang,Zhi-Yong Zhou,Ming-Rong Zhang,Lan-Lan Dai,Xiu-Min Yang and Wei Li |
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刊物名称: | Journal of Investigative Dermatology |
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摘要: | Oculocutaneous albinism (OCA) is a heterogeneous and autosomal recessive disorder with hypopigmentation in eye, hair and skin color. Four genes, TYR, OCA2, TYRP1 and SLC45A2, have been identified as causative genes for non-syndromic OCA1-4 respectively. The genetics identity of OCA5 locus on 4q24 is unknown. Additional unknown OCA genes may exist as at least 5% of OCA patients have not been characterized during mutational screening in several populations. We here used exome sequencing with a family-based recessive mutation model to determine that SLC24A5 is a previously unreported candidate gene for non-syndromic OCA, which we designate as OCA6. Two deleterious mutations in this patient, c.591G>A and c.1361insT, were identified. We found apparent increase of immature melanosomes and less mature melanosomes in the patient’s skin melanocytes. However, no defects in the platelet dense granules were observed, excluding it from typical Hermansky-Pudlak syndrome (HPS), a well-known syndromic OCA. Moreover, the SLC24A5 protein was reduced in steady-state levels in mouse HPS mutants with deficiencies in BLOC-1 and BLOC-2. Our results suggest that SLC24A5 is a previously unreported non-syndromic OCA candidate gene and that the SLC24A5 transporter is transported into mature melanosomes by HPS protein complexes. |