Cellular and molecular defects in a patient with Hermansky-Pudlak syndrome type 5
| Autor: | Laryssa A. Huryn, Tadafumi Yokoyama, Elena-Raluca Nicoli, Bernadette R. Gochuico, Kevin J. O'Brien, Dong Chen, Brian P. Brooks, David R. Adams, Steve Titus, Nathanial J. Tolman, Joshi Stephen, William A. Gahl, May Christine V. Malicdan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proband Viral Diseases lcsh:Medicine Artificial Gene Amplification and Extension medicine.disease_cause Polymerase Chain Reaction White Blood Cells 0302 clinical medicine Animal Cells hemic and lymphatic diseases Medicine and Health Sciences Alveolar Macrophages lcsh:Science Connective Tissue Cells Staining Mutation Multidisciplinary integumentary system Cell Staining Oculocutaneous albinism Phenotypes Infectious Diseases Connective Tissue Hermanski-Pudlak Syndrome 030220 oncology & carcinogenesis Cellular Structures and Organelles Cellular Types Anatomy Research Article Neglected Tropical Diseases Albinism Immune Cells Immunology HPS5 Biology Hantavirus Pulmonary Syndrome Research and Analysis Methods 03 medical and health sciences Organelle medicine Intronic Mutation Genetics Humans Molecular Biology Techniques Molecular Biology Blood Cells lcsh:R Biology and Life Sciences Cell Biology Fibroblasts medicine.disease Tropical Diseases Molecular biology eye diseases Bleeding diathesis 030104 developmental biology Biological Tissue Specimen Preparation and Treatment lcsh:Q Hermansky–Pudlak syndrome Lysosomes |
| Zdroj: | PLoS ONE, Vol 12, Iss 3, p e0173682 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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