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- Title
Cellular and molecular defects in a patient with Hermansky-Pudlak syndrome type 5.
- Authors
Stephen, Joshi; Yokoyama, Tadafumi; Tolman, Nathanial J.; O’Brien, Kevin J.; Nicoli, Elena-Raluca; Brooks, Brian P.; Huryn, Laryssa; Titus, Steven A.; Adams, David R.; Chen, Dong; Gahl, William A.; Gochuico, Bernadette R.; Malicdan, May Christine V.
- 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.
- Subjects
HERMANSKY-Pudlak syndrome; MOLECULAR pathology; CELLULAR pathology; GENETIC disorders; PULMONARY fibrosis
- Publication
PLoS ONE, 2017, Vol 12, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0173682