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PLoS One. 2017 Mar 15;12(3):e0173682. doi: 10.1371/journal.pone.0173682. eCollection 2017.

Cellular and molecular defects in a patient with Hermansky-Pudlak syndrome type 5.

Author information

1
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
2
NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, United States of America.
3
Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
4
Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
5
Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
6
Division of Hematopathology, Mayo Clinic, Rochester, Minnesota, United States of America.

Abstract

Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of genetic disorders typically manifesting with tyrosinase-positive oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis, in some subtypes. Most HPS subtypes are associated with defects in Biogenesis of Lysosome-related Organelle Complexes (BLOCs), which are groups of proteins that function together in the formation and/or trafficking of lysosomal-related endosomal compartments. BLOC-2, for example, consists of the proteins HPS3, HPS5, and HPS6. Here we present an HPS patient with defective BLOC-2 due to a novel intronic mutation in HPS5 that activates a cryptic acceptor splice site. This mutation leads to the insertion of nine nucleotides in-frame and results in a reduced amount of HPS5 at the transcript and protein level. In studies using skin fibroblasts derived from the proband and two other individuals with HPS-5, we found a perinuclear distribution of acidified organelles in patient cells compared to controls. Our results suggest the role of HPS5 in the endo-lysosomal dynamics of skin fibroblasts.

PMID:
28296950
PMCID:
PMC5351877
DOI:
10.1371/journal.pone.0173682
[Indexed for MEDLINE]
Free PMC Article

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