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

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


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.

MeSH terms

  • Hermanski-Pudlak Syndrome / genetics
  • Hermanski-Pudlak Syndrome / pathology*
  • Humans
  • Mutation

Grants and funding

This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Eye Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.