Novel HPS6 mutations identified by whole-exome sequencing in two Japanese sisters with suspected ocular albinism

• Published in: Journal of human genetics 2016-09, Vol.61 (9), p.839-842
• Main Authors: Miyamichi, Daisuke, Asahina, Miki, Nakajima, Junya, Sato, Miho, Hosono, Katsuhiro, Nomura, Takahito, Negishi, Takashi, Miyake, Noriko, Hotta, Yoshihiro, Ogata, Tsutomu, Matsumoto, Naomichi
• Format: Article
• Language: English
• Subjects: Albinism, Ocular - diagnosis; Albinism, Ocular - genetics; Alleles; Child, Preschool; Exome; Female; Fluorescein Angiography; Genes, Recessive; Genotype; High-Throughput Nucleotide Sequencing; Humans; Intracellular Signaling Peptides and Proteins - genetics; Japan; Mutation; Pedigree; Phenotype; Siblings; Tomography, Optical Coherence
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2016.56

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction and ceroid deposition. We report suspected ocular albinism in two Japanese sisters, caused by mutations in the HPS6 (Hermansky-Pudlak syndrome 6) gene. Trio-based whole-exome sequencing (WES) identified novel compound heterozygous mutations in HPS6 (c.1898delC: mother origin and c.2038C>T: father origin) in the two sisters. To date, 10 associated mutations have been detected in HPS6. Although we detected no general manifestations, including platelet dysfunction, in the sisters, even in long-term follow-up, we established a diagnosis of HPS type 6 based on the HPS6 mutations and absence of dense bodies in the platelets, indicating that WES can identify cases of HPS type 6. To the best of our knowledge, this is the first report of HPS6 mutations in Japanese patients.