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Ann Med 2019 Apr 16:1-8. Epub 2019 Apr 16.

c Department of Hematology and Oncology, University Hospital of Morales Meseguer, Centro Regional de Hemodonación, University of Murcia , Murcia , Spain.

Background: Hermansky-Pudlak syndrome (HPS) is a rare inherited platelet disorder characterized by bleeding diathesis, oculocutaneous albinism (OCA) and a myriad of often-serious clinical complications.

Methods: We established the clinical and laboratory phenotype and genotype of six unrelated pedigrees comprising ten patients with clinical suspicion of HPS; including platelet aggregation, flow cytometry, platelet dense granule content, electron microscopy and high-throughput sequencing (HTS).

Results: The clinical presentation showed significant heterogeneity and no clear phenotype-genotype correlations. Read More

Am J Respir Crit Care Med 2019 Apr 15. Epub 2019 Apr 15.

Indiana University School of Medicine, 12250, Medicine, Indianapolis, Indiana, United States.

J Allergy Clin Immunol Pract 2019 Apr 8. Epub 2019 Apr 8.

Department of Pediatrics, Fondazione MBBM, University of Milano-Bicocca, Monza, Italy.

Traffic 2019 Apr 4. Epub 2019 Apr 4.

Dept. of Pathology & Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104.

Lysosome-related organelles comprise a diverse group of cell type-specific, membrane-bound subcellular organelles that derive at least in part from the endolysosomal system but that have unique contents, morphology, and functions to support specific physiological roles. They include melanosomes that provide pigment to our eyes and skin, alpha and dense granules in platelets and lytic granules in cytotoxic T cells and natural killer cells that release effectors to regulate hemostasis and immunity, and distinct classes of lamellar bodies in lung epithelial cells and keratinocytes that support lung plasticity and skin lubrication. The formation, maturation and/or secretion of subsets of lysosome-related organelles are dysfunctional or entirely absent in a number of hereditary syndromic disorders, including in particular the Hermansky-Pudlak syndromes. Read More

Nature 2019 Apr 3. Epub 2019 Apr 3.

Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.

Current programmable nuclease-based methods (for example, CRISPR-Cas9) for the precise correction of a disease-causing genetic mutation harness the homology-directed repair pathway. However, this repair process requires the co-delivery of an exogenous DNA donor to recode the sequence and can be inefficient in many cell types. Here we show that disease-causing frameshift mutations that result from microduplications can be efficiently reverted to the wild-type sequence simply by generating a DNA double-stranded break near the centre of the duplication. Read More

Ultrastruct Pathol 2019 Apr 1:1-5. Epub 2019 Apr 1.

b Department of Histology, Cerrahpasa Faculty of Medicine , Istanbul University-Cerrahpasa , Istanbul , Turkey.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder consisting of oculocutaneous albinism, platelet storage pool deficiency, and lysosomal accumulation of ceroid lipofuscin. The storage pool deficiency of HPS is associated with the lack of dense bodies in the platelets, resulting in impaired response in the secondary phase of aggregation. Patients with HPS have normal coagulation tests; however, their bleeding time is usually prolonged despite normal or increased platelet counts. Read More

J Biol Chem 2019 Mar 5. Epub 2019 Mar 5.

Department of Integrative Life Sciences, Tohoku University, Graduate School of Life Sciences, Japan.

() is one of the genes whose mutations have been associated with Hermansky-Pudlak syndrome (HPS), characterized by ocular albinism and a susceptibility to bleeding because of defects in the biogenesis of lysosome-related organelles such as melanosomes. HPS4 protein forms a BLOC-3 complex with HPS1, another gene product, and the complex has been proposed to function as a guanine nucleotide exchange factor (GEF) for RAB32, a member of the Rab small GTPase family (Rab32), and Rab38 (Rab32/38-GEF) and also as a Rab9 effector. Although both Rab32/38 and Rab9 have previously been shown to be involved in melanogenesis in mammalian epidermal melanocytes, the functional relationships of these small GTPases with BLOC-3 remain unknown. Read More

World J Gastroenterol 2019 Feb;25(8):1031-1036

Institut des Maladies de l'Appareil Digestif, Department of Gastroenterology and Digestive Oncology, Nantes University Hospital, Nantes Cedex 44093, France.

Background: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage pool deficiency and systemic complications associated with ceroid deposition in the reticuloendothelial system. HPS types 1 and 4 are associated with Crohn's disease (CD)-like gastrointestinal disorders, such as granulomatous enterocolitis or perianal disease. Cases of colitis can be particularly severe and, before the use of anti-tumor necrosis factor alpha (TNFα) therapy had become common, were reported as showing poor responsiveness to medical treatment. Read More

Orphanet J Rare Dis 2019 02 21;14(1):52. Epub 2019 Feb 21.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1851, Bethesda, MD, 20892-1851, USA.

Background: Determining the etiology of oculocutaneous albinism is important for proper clinical management and to determine prognosis. The purpose of this study was to genotype and phenotype eight adopted Chinese children who presented with oculocutaneous albinism and easy bruisability.

Results: The patients were evaluated at a single center; their ages ranged from 3 to 8 years. Read More

Reprod Fertil Dev 2019 Feb 21. Epub 2019 Feb 21.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. Pale ear (ep) and pearl (pe) mice, bearing mutations in the biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (Ap3b1) genes respectively, are mouse models of human HPS Type 1 (HPS1) and Type 2 (HPS2) respectively. In the present study we investigated and compared the reduced fertilities of ep and pe male mice. Read More

Stem Cell Reports 2019 Mar 14;12(3):431-440. Epub 2019 Feb 14.

Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. Read More

Ophthalmic Genet 2019 Feb 4;40(1):83-85. Epub 2019 Feb 4.

b Hamilton Eye Institute, Department of Ophthalmology , University of Tennessee , Memphis , TN , USA.

Biosci Rep 2019 Feb 19;39(2). Epub 2019 Feb 19.

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; Genetics and Birth Defects Control Center, National Center for Children's Health; MOE Key Laboratory of Major Diseases in Children; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China

Atherosclerosis is characterized by the accumulation of lipid-rich plaques in the arterial wall. Its pathogenesis is very complicated and has not yet been fully elucidated. It is known that dyslipidemia is a major factor in atherosclerosis. Read More

Toxicon 2019 Mar 21;159:50-60. Epub 2019 Jan 21.

Instituto Butantan, Laboratório de Fisiopatologia, Av. Dr. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil; Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address:

Victims of Bothrops jararaca snakebites manifest bleedings, blood incoagulability, platelet dysfunction, and thrombocytopenia, and the latter has been directly implicated in the genesis of hemorrhagic diathesis. We addressed herein the direct effects of B. jararaca venom (BjV) on ex vivo platelet aggregation and granule secretion in washed human and mouse platelets. Read More

Eur J Haematol 2019 May 6;102(5):432-436. Epub 2019 Mar 6.

Department of Surgery, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico.

Introduction: The Hermansky-Pudlak syndrome (HPS) is an autosomal recessive rare disorder characterized by oculocutaneous albinism, bleeding diathesis, chronic granulomatous colitis and/or pulmonary fibrosis. HPS is the most common single-gene disorder in Puerto Rico with a prevalence of 1:1,800 in the Northwest of the island. Risk of menorrhagia and post-partum hemorrhage (PPH) in cases of women with HPS have been described in the medical literature, but data regarding comprehensive description of bleeding diathesis remains lacking. Read More

BMC Gastroenterol 2019 Jan 11;19(1). Epub 2019 Jan 11.

Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.

Background: Hermansky-Pudlak syndrome (HPS) is a rare, genetically heterogeneous disorder that manifests oculocutaneous albinism together with bleeding diatheses that reflect a platelet storage pool deficiency. Ten genetic subtypes of this autosomal recessive condition have been described to date. Some patients with Hermansky-Pudlak syndrome type 1, 4, or 6 develop Crohn's-like inflammatory bowel disease at any age including early childhood, but most often in adolescence or young adulthood. Read More

Haematologica 2019 Jan 10. Epub 2019 Jan 10.

ErasmusMC, University Medical Center Rotterdam

Weibel-Palade bodies are endothelial secretory organelles that contain von Willebrand factor, P-selectin and CD63. Release of von Willebrand factor from Weibel-Palade bodies is crucial for platelet adhesion during primary hemostasis. Endosomal trafficking of proteins like CD63 to Weibel-Palade bodies during maturation is dependent on the adaptor protein complex 3 complex. Read More

J Innate Immun 2019 17;11(2):168-180. Epub 2018 Dec 17.

Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Platelet-dense (δ) granules are important for platelet function. Platelets contribute to host defense and vascular integrity during pneumonia and sepsis, and δ granule products, including adenosine diphosphate (ADP), can influence inflammatory responses. We therefore aimed to study the role of platelet δ granules in the host response during sepsis. Read More

Eur J Med Genet 2018 Nov 22. Epub 2018 Nov 22.

Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman; Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman. Electronic address:

Several types of Hermansky-Pudlak syndromes (HPS) represent a group of immunodeficiency syndromes that feature both leukocyte defects with partial albinism of hair, skin, and eyes. These conditions share defects in genes that encode proteins involved in the biogenesis, function, and trafficking of secretory lysosomes. Mutations in AP3D1 which encode the main subunit AP-3(δ) were recently reported on one individual and led to Hermansky-Pudlak Syndrome type 10 (HPS10; OMIM 617050). Read More

Nature 2018 11 7;563(7733):646-651. Epub 2018 Nov 7.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Following Cas9 cleavage, DNA repair without a donor template is generally considered stochastic, heterogeneous and impractical beyond gene disruption. Here, we show that template-free Cas9 editing is predictable and capable of precise repair to a predicted genotype, enabling correction of disease-associated mutations in humans. We constructed a library of 2,000 Cas9 guide RNAs paired with DNA target sites and trained inDelphi, a machine learning model that predicts genotypes and frequencies of 1- to 60-base-pair deletions and 1-base-pair insertions with high accuracy (r = 0. Read More

Pigment Cell Melanoma Res 2018 Nov 2. Epub 2018 Nov 2.

Beijing Key Laboratory for Genetics of Birth Defects; MOE Key Laboratory of Major Diseases in Children, Center for Medical Genetics, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by oculocutaneous albinism (OCA) or ocular albinism (OA), bleeding tendency and other symptoms due to multiple defects in tissue-specific lysosome-related organelles. Ten HPS subtypes have been characterized with mutations in HPS1 to HPS10, which encode the subunits of BLOC-1, -2, -3, and AP-3. Using next-generation sequencing (NGS), we have screened 100 hypopigmentation genes in OCA or OA patients and identified four HPS-1, one HPS-3, one HPS-4, one HPS-5, and three HPS-6. Read More

Am J Med Genet A 2018 Dec 4;176(12):2819-2823. Epub 2018 Oct 4.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.

Heřmanský-Pudlák syndrome (HPS), a rare autosomal recessive disorder, manifests with oculocutaneous albinism and a bleeding diathesis. However, severity of disease can be variable and is typically related to the genetic subtype of HPS; HPS type 6 (HPS-6) is an uncommon subtype generally associated with mild disease. A Caucasian adult female presented with a history of severe bleeding; ophthalmologic examination indicated occult oculocutaneous albinism. Read More

BMJ Case Rep 2018 Oct 12;2018. Epub 2018 Oct 12.

Royal College of Surgeons in Ireland, Dublin, Ireland.

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder characterised by oculocutaneous albinism, bleeding diathesis and end-stage renal disease (ESRD), due to interstitial deposition of ceroid lipofuscin. Renal transplantation is potentially a definitive treatment option for patients with ESRD due to HPS. Herein, we describe the case of a 55-year-old male patient with HPS that successfully underwent a living donor kidney transplant. Read More

iScience 2018 Aug 26;6:199-211. Epub 2018 Jul 26.

Biotechnology Center, Technische Universität Dresden, Tatzberg 47-51, Dresden 01307, Germany. Electronic address:

Bone-resorbing osteoclasts play a central role in bone remodeling and its pathology. To digest bone, osteoclasts re-organize both F-actin, to assemble podosomes/sealing zones, and membrane traffic, to form bone-facing ruffled borders enriched in lysosomal membrane proteins. It remains elusive how these processes are coordinated. Read More

Biosci Rep 2018 10 7;38(5). Epub 2018 Sep 7.

Beijing Key Laboratory for Genetics of Birth Defects, MOE Key Laboratory of Major Diseases in Children, Center for Medical Genetics, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China

Platelets respond to vascular injury via surface receptor stimulation and signaling events to trigger aggregation, procoagulant activation, and granule secretion during hemostasis, thrombosis, and vascular remodeling. Platelets contain three major types of secretory granules including dense granules (or δ-granules, DGs), α-granules (AGs), and lysosomes. The contents of platelet granules are specific. Read More

Int J Mol Sci 2018 Jul 27;19(8). Epub 2018 Jul 27.

Department of Life Science, Medical Research Institute, Kanazawa Medical University, 1-1 Uchinada-Daigaku, Kahokugun, Ishikawa 920-0293, Japan.

is highly expressed in alveolar type II cells, melanocytes, and platelets. These cells are specifically-differentiated cells and contain characteristic intracellular organelles called lysosome-related organelles, i.e. Read More

Mol Genet Metab 2018 09 23;125(1-2):168-173. Epub 2018 Jul 23.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Purpose: Limited information is available regarding chronic treatment with pirfenidone, an anti-fibrotic drug. Effects of long-term open-label pirfenidone were evaluated in a small cohort with Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder with highly penetrant pulmonary fibrosis.

Results: Three patients with HPS pulmonary fibrosis treated with open-label pirfenidone and twenty-one historical controls randomized to placebo were studied at a single center. Read More

Eur Respir Rev 2018 Sep 11;27(149). Epub 2018 Jul 11.

Interstitial Lung Disease Center of Excellence, Dept of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands

Fibrotic interstitial pneumonias are a group of rare diseases characterised by distortion of lung interstitium. Patients with mutations in surfactant-processing genes, such as surfactant protein C (), surfactant protein A1 and A2 ( and ), ATP binding cassette A3 () and Hermansky-Pudlak syndrome (, and ), develop progressive pulmonary fibrosis, often culminating in fatal respiratory insufficiency. Although many mutations have been described, little is known about the optimal treatment strategy for fibrotic interstitial pneumonia patients with surfactant-processing mutations. Read More

Thorax 2018 11 25;73(11):1085-1088. Epub 2018 Jun 25.

Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the gene. Read More

Ophthalmic Genet 2018 08 21;39(4):450-456. Epub 2018 May 21.

a Department of Ophthalmology , Hadassah-Hebrew University Medical Center , Jerusalem , Israel.

Background: In developed countries, genetically inherited eye diseases are responsible for a high percentage of childhood visual impairment. We aim to report our experience using preimplantation genetic diagnostics (PGD) in order to avoid transmitting a genetic form of eye disease associated with childhood visual impairment and ocular cancer.

Material And Methods: Retrospective case series of women who underwent in vitro fertilization (IVF) and PGD due to a familial history of inherited eye disease and/or ocular cancer, in order to avoid having a child affected with the known familial disease. Read More

Exp Oncol 2018 Mar;40(1):73-78

State Institution "Institute of Hereditary Pathology of National Academy of Medical Sciences of Ukraine", Lviv 79008, Ukraine.

Aim: To study the relationship between the genotype and the phenotype in the patients with Hermansky - Pudlak syndrome (HPS) associated with granulomatous colitis; to monitor clinical course of the disease for adequate treatment, cancer surveillance and genetic counseling.

Materials And Methods: The diagnosis of HPS is established by physical examination, chest X-ray, computed tomography, endoscopic examination with biopsy, and laboratory tests, including histology, baseline laboratory blood, urine and feces tests, determination of ASCA-C and ANCA antibodies using an ELISA. Molecular genetic testing for HPS gene mutations, R702W, G908R, L1007fs and P268S mutations in NOD2 gene, and TaqI variant of the VDR gene were carried out. Read More

Orphanet J Rare Dis 2018 03 27;13(1):42. Epub 2018 Mar 27.

Ludwig-Maximilians University, Dr von Haunersches Kinderspital, German Center for Lung Research (DZL), Lindwurmstr. 4, 80337, Munich, Germany.

Background: Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia and knowledge of its pulmonary phenotype in children is scarce.

Methods: Six children with genetically proven HPS-2 presented to the chILD-EU register between 2009 and 2017; the data were collected systematically and imaging studies were scored blinded. Read More

PLoS One 2018 16;13(3):e0194193. Epub 2018 Mar 16.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Read More

Front Immunol 2018 31;9:76. Epub 2018 Jan 31.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.

The immunome (immune cell phenotype, gene expression, and serum cytokines profiling) in pulmonary fibrosis is incompletely defined. Studies focusing on inherited forms of pulmonary fibrosis provide insights into mechanisms of fibrotic lung disease in general. To define the cellular and molecular immunologic phenotype in peripheral blood, high-dimensional flow cytometry and large-scale gene expression of peripheral blood mononuclear cells and serum proteomic multiplex analyses were performed and compared in a cohort with familial pulmonary fibrosis (FPF), an autosomal dominant disorder with incomplete penetrance; Hermansky-Pudlak syndrome pulmonary fibrosis (HPSPF), a rare autosomal recessive disorder; and their unaffected relatives. Read More

J Immunol 2018 03 2;200(6):2140-2153. Epub 2018 Feb 2.

Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912;

Hermansky-Pudlak syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in HPS-1 and HPS-4 patients. However, the mechanisms that underlie the exaggerated injury and fibroproliferative repair responses in HPS have not been adequately defined. Read More

J Exp Biol 2018 03 19;221(Pt 6). Epub 2018 Mar 19.

Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, C.P. 07360, México

Membrane transporters and sequestration mechanisms concentrate metal ions differentially into discrete subcellular microenvironments for use in protein cofactors, signalling, storage or excretion. Here we identify zinc storage granules as the insect's major zinc reservoir in principal Malpighian tubule epithelial cells of The concerted action of Adaptor Protein-3, Rab32, HOPS and BLOC complexes as well as of the white-scarlet (ABCG2-like) and ZnT35C (ZnT2/ZnT3/ZnT8-like) transporters is required for zinc storage granule biogenesis. Due to lysosome-related organelle defects caused by mutations in the homologous human genes, patients with Hermansky-Pudlak syndrome may lack zinc granules in beta pancreatic cells, intestinal paneth cells and presynaptic vesicles of hippocampal mossy fibers. Read More

Genetics 2018 03 16;208(3):1131-1146. Epub 2018 Jan 16.

Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China

Hermansky-Pudlak syndrome (HPS) is a human autosomal recessive disorder that is characterized by oculocutaneous albinism and a deficiency of the platelet storage pool resulting from defective biogenesis of lysosome-related organelles (LROs). To date, 10 HPS genes have been identified, three of which belong to the octamer complex BLOC-1 (biogenesis of lysosome-related organelles complex 1). One subunit of the BLOC-1 complex, BLOS1, also participates in the BLOC-1-related complex (BORC). Read More

Am J Respir Cell Mol Biol 2018 May;58(5):566-574

1 Division of Neonatology and.

Defining the mechanisms of cellular pathogenesis in rare lung diseases such as Hermansky-Pudlak syndrome (HPS) is often complicated by loss of the differentiated phenotype of cultured primary alveolar type 2 (AT2) cells, as well as by a lack of durable cell lines that are faithful to both AT2-cell and rare disease phenotypes. We used CRISPR/Cas9 gene editing to generate a series of HPS-specific mutations in the MLE-15 cell line. The resulting MLE-15/HPS cell lines exhibit preservation of AT2 cellular functions, including formation of lamellar body-like organelles, complete processing of surfactant protein B, and known features of HPS specific to each trafficking complex, including loss of protein targeting to lamellar bodies. Read More

Blood Cells Mol Dis 2018 03 31;69:113-116. Epub 2017 Oct 31.

Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

Platelets 2018 Jan 1;29(1):91-94. Epub 2017 Nov 1.

a Division of Hematology, Department of Medicine , Mayo Clinic , Rochester , MN , USA.

Hermansky-Pudlak syndrome (HPS) - characterized by the distinct clinical phenotypes of both oculocutaneous albinism and mild bleeding diathesis-is caused by mutations in genes that have crucial roles in the assembly of cellular organelles (skin melanosomes, platelet delta [dense] granules, lung lamellar bodies, and cytotoxic T-cell lymphocyte granules). Immunodeficiency, pulmonary fibrosis and granulomatous colitis are associated with some, but not all subtypes of HPS, with varying degrees of clinical severity. We describe a patient diagnosed with platelet dense granule storage pool deficiency (DG-SPD) at age 38 years after he presented with spontaneous intracranial hemorrhage. Read More

Pigment Cell Melanoma Res 2018 03 2;31(2):267-276. Epub 2017 Nov 2.

Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), a bleeding tendency, and ceroid deposition. Most of the causative genes for HPS encode subunits of the biogenesis of lysosome-related organelles complex (BLOC). In this study, we identified one patient each with HPS4, HPS6, and HPS9 by whole-exome sequencing. Read More

Pediatr Dermatol 2017 Nov 16;34(6):638-646. Epub 2017 Oct 16.

Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder caused by mutations in one of nine genes involved in the packaging and formation of specialized lysosomes, including melanosomes and platelet-dense granules. The cardinal features are pigmentary dilution, bleeding diathesis, and accumulation of ceroid-like material in reticuloendothelial cells. Pulmonary fibrosis induced by tissue damage is seen in the most severe forms, and one subtype is characterized by immunodeficiency. Read More

G3 (Bethesda) 2017 09 7;7(9):3123-3131. Epub 2017 Sep 7.

Department of Molecular and Cell Biology, University of California-Berkeley, California 94720

Here, we present and characterize the spontaneous X-linked recessive mutation , which causes oculocutaneous albinism in threespine sticklebacks (). In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO), the melanosome. mutants display not only reduced pigmentation of melanosomes in melanophores, but also reductions in the iridescent silver color from iridophores, while the yellow pigmentation from xanthophores appears unaffected. Read More

Presse Med 2017 Jul - Aug;46(7-8 Pt 1):648-654. Epub 2017 Jul 19.

CHU de Bordeaux, service de dermatologie, 33076 Bordeaux, France.

Albinism is a genetic disease affecting 1/17,000 person worldwide. It constitutes the second cause of congenital loss of visual acuity after optic atrophy. Albinism is heterogeneous both at the clinical and genetic levels. Read More

Pigment Cell Melanoma Res 2017 Jan 20;30(6):563-570. Epub 2017 Oct 20.

Service Génétique Médicale, CHU de Bordeaux, Bordeaux, France.

Hermansky-Pudlak syndrome (HPS), first described in 1959, is a rare form of syndromic oculocutaneous albinism associated with bleeding diathesis and in some cases pulmonary fibrosis and granulomatous colitis. All 10 HPS types are caused by defects in vesicle trafficking of lysosome-related organelles (LRO) proteins. The HPS5 protein associates with HPS3 and HPS6 to form the biogenesis of lysosome-related organelles complex-2 (BLOC-2). Read More

Hum Mutat 2017 10 15;38(10):1402-1411. Epub 2017 Jun 15.

Sanquin Research, and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.

Hermansky-Pudlak syndrome type 2 (HPS2) is a syndrome caused by mutations in the beta-3A subunit of the adaptor protein (AP)-3 complex (AP3B1 gene). We describe five unreported cases with four novel mutations, one of which caused aberrant pre-mRNA splicing. A point mutation c. Read More

Am J Hum Genet 2017 05;100(5):837

Respir Res 2017 04 24;18(1):70. Epub 2017 Apr 24.

Department of Respiratory Medicine, Kanazawa Medical University, 1-1 Uchinada-Daigaku, Kahokugun, Ishikawa, 920-0293, Japan.

Background: Rab8 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. Ruby rats carrying Rab8 and other gene mutations exhibit oculocutaneous albinism, bleeding diathesis, and hence, are a rat model of human Hermansky-Pudlak syndrome (HPS). We previously showed that Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar type II cells. Read More