Figures
- FIGURE 1
Clinical features of Hermansky–Pudlak syndrome (HPS). a, b) Hypopigmentation of a) hair and b) skin and iris of a Puerto Rican male. c) δ-granules are absent in platelets from a patient with HPS-1 imaged using whole-mount transmission electron microscopy. Scale bar: 2 μm. d) Bilateral interstitial infiltrates are found in a chest radiograph of a 50-year-old female with HPS pulmonary fibrosis. e) Fibrotic lung tissue stained with haematoxylin and eosin and f) unstained renal epithelial cells isolated from urine derived from a subject with HPS-1 show abnormal intracellular deposits. Scale bar: 20 μm.
- FIGURE 2
Relationships of protein complexes involved in Hermansky–Pudlak syndrome (HPS), biogenesis of intracellular organelles and clinical manifestations of disease. Four stages (I–IV) of melanosome maturation and platelet δ-granule (dense granule), lamellar body and lysosome formation via the endosomal pathway from the TGN are shown. Defects in these vesicles are associated with oculocutaneous albinism, bleeding diathesis, pulmonary fibrosis and excessive cellular deposits in HPS. Protein complexes associated with HPS, including AP-3, BLOC-1, BLOC-2 and BLOC-3, and a Rab32/38 guanine nucleotide exchange factor comprised of HPS1 and HPS4 protein subunits, are involved in the formation of melanosomes, platelet δ-granules, lamellar bodies and lysosomes. TGN: trans-Golgi network; AP: adaptor protein; BLOC: biogenesis of lysosome-related organelles complex.
- FIGURE 3
Computed tomography (CT) scan and histopathological images of Hermansky–Pudlak syndrome (HPS) pulmonary fibrosis. a) Supine and b) prone CT scan images of a 47-year-old subject with moderate HPS pulmonary fibrosis show bilateral ground-glass opacities, reticulations and honeycombing. c) CT scan image of a 38-year-old subject with HPS pulmonary fibrosis demonstrates bilateral ground-glass opacities, traction bronchiectasis, reticulations and honeycombing. d) Aggregates of foamy alveolar macrophages, vacuolated hyperplastic type II alveolar epithelial cells containing enlarged lamellar bodies, and interstitial accumulation of cells and extracellular matrix are found in lung tissue from a subject with HPS pulmonary fibrosis. Haematoxylin and eosin staining. Scale bar: 20 μm.
Tables
- TABLE 1
Hermansky–Pudlak syndrome (HPS)-associated genes, loci, proteins and complexes
HPS type Gene# Locus Protein Complex HPS-1 HPS1 10q23.1 HPS1 BLOC-3 HPS-2 AP3B1 5q14.1 AP-3 complex β3A subunit AP-3 HPS-3 HPS3 3q24 HPS3 BLOC-2 HPS-4 HPS4 22q11.2–q12.2 HPS4 BLOC-3 HPS-5 HPS5 11p15–p13 HPS5 BLOC-2 HPS-6 HPS6 10q24.3 HPS6 BLOC-2 HPS-7 DTNBP1 6p22.3 Dysbindin BLOC-1 HPS-8 BLOC1S3 19q13 BLOC-1 subunit 3 BLOC-1 HPS-9 PLDN 15q15 Pallidin BLOC-1 HPS-10 AP3D1 19p13.3 AP-3 complex δ1 subunit AP-3 AP: adaptor protein; BLOC: biogenesis of lysosome-related organelles complex. #: see www.genecards.org for aliases.
- TABLE 2
Clinical features of Hermansky–Pudlak syndrome (HPS) pulmonary fibrosis and idiopathic pulmonary fibrosis (IPF)
HPS-1 or HPS-4 pulmonary fibrosis HPS-2 pulmonary fibrosis IPF Onset of pulmonary symptoms Middle age Children or young adults >50 years of age Acute exacerbations Yes Unknown Yes Oculocutaneous albinism Yes Yes No Nystagmus Yes Yes No Excessive bleeding Yes Yes No HRCT scan finding of ground-glass opacification Yes Yes No Type II epithelial cell enlargement Yes Yes No Giant lamellar bodies Yes Yes No Foamy alveolar macrophages Yes Unknown No Ceroid lipofuscin tissue deposition Yes Yes No Pulmonary histopathology UIP, NSIP, DAD UIP, NSIP, DIP UIP HRCT: high-resolution computed tomography; UIP: usual interstitial pneumonia; NSIP: nonspecific interstitial pneumonia; DAD: diffuse alveolar damage; DIP: desquamative interstitial pneumonitis.
