Exome Sequencing Identifies SLC24A5 as a Candidate Gene for Nonsyndromic Oculocutaneous Albinism

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:133

Article

Wei, Ai-Hua^1,2  Zang, Dong-Jie¹  Zhang, Zhe¹  Liu, Xuan-Zhu³  He, Xin¹  Yang, Lin¹  Wang, Yi¹  Zhou, Zhi-Yong¹  Zhang, Ming-Rong³  Dai, Lan-Lan³  Yang, Xiu-Min²  Li, Wei¹ 

[1] Chinese Acad Sci, State Key Lab Mol Dev Biol, Inst Genet & Dev Biol, Beijing 100101, Peoples R China

[2] Capital Med Univ, Dept Dermatol, Beijing Tongren Affiliated Hosp, Beijing 100730, Peoples R China

[3] Beijing Genom Inst Shenzhen, Shenzhen, Peoples R China

DOI  :  10.1038/jid.2013.49

来源: Elsevier

【 摘 要 】

Oculocutaneous albinism (OCA) is a heterogeneous and autosomal recessive disorder with hypopigmentation in the eye, hair, and skin color. Four genes, TYR, OCA2, TYRP1, and SLC45A2, have been identified as causative genes for nonsyndromic OCA1-4, respectively. The genetic 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 used exome sequencing with a family-based recessive mutation model to determine that SLC24A5 is a previously unreported candidate gene for nonsyndromic 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 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 nonsyndromic OCA candidate gene and that the SLC24A5 transporter is transported into mature melanosomes by HPS protein complexes.

【 授权许可】

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