A novel BLOC1S5‐related HPS‐11 patient and zebrafish with bloc1s5 disruption

다국어 초록 (Multilingual Abstract)

Hermansky–Pudlak Syndrome (HPS) cases present with a variable degree of OCA and bleeding tendency. HPS is categorized into eleven types based on eleven causative genes, and disease severity varies among different types. By whole‐exome sequencing performed on a family trio and Sanger sequencing of candidate variants, we identified a novel homozygous variant (NM_201280.3: c.181delC, p.Val61*) in BLOC1S5 in the patient who presents OCA and mild bleeding diathesis, and his healthy parents are heterozygous carriers. The variant can be considered pathogenic based on the guideline American College of Medical Genetics and Genomics, and the patient is proposed to be affected with HPS‐11. In this study, we also explored bloc1s5 in zebrafish. bloc1s5 mRNA can be detected during early development of zebrafish. bloc1s5 knockdown zebrafish present with retinal hypopigmentation, thrombocytes loss and pericardial edema, and dll4/notch1 signaling and vascular integrity signaling are down‐regulated at mRNA level in bloc1s5 morphants. The data from the first HPS‐11 patient in Chinese population expand phenotypic and genotypic spectrum of HPS‐11. Disruption of bloc1s5 in zebrafish recapitulates HPS‐11‐like phenotypes, and the potential signaling pathways associated with bloc1s5 are proposed. Altogether, this study may facilitate genetic counseling of HPS and investigation about BLOC1S5.