G3 (Bethesda) 2017 Sep 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 casper, which causes oculocutaneous albinism in threespine sticklebacks (Gasterosteus aculeatus). In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO), the melanosome. casper 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 Jun 22. Epub 2017 Jun 22.

Service Génétique Médicale, CHU de Bordeaux, Place Amélie Raba Léon, 33076, 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 lysosomes-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 Oct 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 Apr 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: Rab(3)8 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. Ruby rats carrying Rab(3)8 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

Expert Rev Hematol 2017 May 13;10(5):375-381. Epub 2017 Apr 13.

c MRC Laboratory for Molecular Cell Biology , University College London , London , UK.

Introduction: Platelet granule deficiencies lead to bleeding disorders, but their specific diagnosis typically requires whole mount transmission electron microscopy, which is often not available and has a number of important limitations. We recently proposed the use of advanced forms of fluorescence microscopy - the so-called 'super-resolution' microscopies - as a possible solution. Areas covered: In this special report, we review the diagnosis of platelet granule deficiencies, and discuss how recent developments in fluorescence microscopy may be useful in improving diagnostic approaches to these and related disorders. Read More

PLoS One 2017 15;12(3):e0173682. Epub 2017 Mar 15.

NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, United States of America.

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. Read More

Mol Genet Genomics 2017 Jun 13;292(3):663-670. Epub 2017 Mar 13.

Aquatic Genomics Unit, Fish Molecular Genetics and Biotechnology Laboratory, School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL, 36849, USA.

Albinism is caused by a series of genetic abnormalities leading to reduction of melanin production. Albinism is quite frequent in catfish, but the causative gene and the molecular basis were unknown. In this study, we conducted a genome-wide association study (GWAS) using the 250 K SNP array. Read More

Blood Cells Mol Dis 2017 Mar 6. Epub 2017 Mar 6.

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:

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder causing oculocutaneous albinism, bleeding disorder and ceroid lipofuscinosis. Platelets from HPS patients are characterized by impaired secretion of dense (δ)-bodies (CD63). Meanwhile, there are ten known human HPS genes, each leading to a particular clinical HPS subtype (HPS1-HPS10). Read More

Mol Genet Metab 2017 Apr 27;120(4):378-383. Epub 2017 Feb 27.

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

Purpose: Hermansky-Pudlak syndrome (HPS) is a rare inherited disorder with ten reported genetic types; each type has defects in subunits of either Adaptor Protein-3 complex or Biogenesis of Lysosome-related Organelles Complex (BLOC)-1, -2, or -3. Very few patients with BLOC-1 deficiency (HPS-7, -8, and -9 types) have been diagnosed. We report results of comprehensive clinical testing and molecular analyses of primary fibroblasts from a new case of HPS-7. Read More

ACG Case Rep J 2017 18;4:e14. Epub 2017 Jan 18.

Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a lack of dense granules in platelets. HPS types 1 and 4 are associated with a granulomatous enterocolitis that is phenotypically indistinguishable from Crohn's disease. We present two cases of HPS-associated Crohn's disease phenotype in which the patients were refractory to standard medical management. Read More

J Thromb Haemost 2017 Apr 23;15(4):792-801. Epub 2017 Feb 23.

Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA.

Essentials Platelet dense granule (DG) deficiency is a major abnormality in RUNX1 haplodeficiency patients. The molecular mechanisms leading to the platelet DG deficiency are unknown. Platelet expression of PLDN (BLOC1S6, pallidin), involved in DG biogenesis, is regulated by RUNX1. Read More

Ann Am Thorac Soc 2017 Jan;14(1):152

Am J Clin Pathol 2016 Dec 27;146(6):681-693. Epub 2016 Dec 27.

From the Departments of Medicine

Objectives: The clinical diagnosis of qualitative platelet disorders (QPDs) based on light transmission aggregometry (LTA) requires significant blood volume, time, and expertise, all of which can be barriers to utilization in some populations and settings. Our objective was to develop a more rapid assay of platelet function by measuring platelet-mediated clot contraction in small volumes (35 µL) of whole blood using T2 magnetic resonance (T2MR).

Methods: We established normal ranges for platelet-mediated clot contraction using T2MR, used these ranges to study patients with known platelet dysfunction, and then evaluated agreement between T2MR and LTA with arachidonic acid, adenosine diphosphate, epinephrine, and thrombin receptor activator peptide. Read More

Int J Mol Cell Med 2016 3;5(3):192-195. Epub 2016 Jul 3.

Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Pediatr Blood Cancer 2017 May 4;64(5). Epub 2016 Dec 4.

Institute of Experimental Biomedicine I, University Hospital Würzburg, Germany.

Background: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by oculocutaneous albinism and platelet dysfunction. We report on a novel HPS6 homozygous frameshift variant (c.1919_1920delTC; p. Read More

J Genet Genomics 2016 Dec 21;43(12):686-693. Epub 2016 Oct 21.

Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Pediatric Disease Research, Beijing 100045, China; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100069, China. Electronic address:

Hermansky-Pudlak syndrome (HPS) is a recessive disorder with bleeding diathesis, which has been linked to platelet granule defects. Both platelet granules and endothelial Weibel-Palade bodies (WPBs) are members of lysosome-related organelles (LROs) whose formation is regulated by HPS protein associated complexes such as BLOC (biogenesis of lysosome-related organelles complex) -1, -2, -3, AP-3 (adaptor protein complex-3) and HOPS (homotypic fusion and protein sorting complex). Von Willebrand factor (VWF) is critical to hemostasis, which is stored in a highly-multimerized form as tubules in the WPBs. Read More

Am J Hum Genet 2016 Dec 23;99(6):1368-1376. Epub 2016 Nov 23.

Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université de Bourgogne, 21079 Dijon, France; INSERM 1141, Service de Neurologie Pédiatrique, Hôpital Robert Debré, 75019 Paris, France; Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, Centre Hospitalier Universitaire Dijon, 21079 Dijon, France. Electronic address:

Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. Read More

BMJ Case Rep 2016 Nov 17;2016. Epub 2016 Nov 17.

Department of Obstetrics, UZA, Edegem, Belgium.

We report on the obstetric outcome of a woman aged 27 years with Hermansky-Pudlak syndrome (HPS). She underwent a caesarean section after failed induction of labour. Platelet transfusion was administered in a set schedule for 36 hours, starting 2 hours before delivery. Read More

Platelets 2017 Mar 16;28(2):138-146. Epub 2016 Nov 16.

a Department of Biochemistry and Molecular Biology , Colorado State University , Fort Collins , Colorado , USA.

Platelet dense granules (DGs) are membrane bound compartments that store polyphosphate and small molecules such as ADP, ATP, Ca(2+), and serotonin. The release of DG contents plays a central role in platelet aggregation to form a hemostatic plug. Accordingly, congenital deficiencies in the biogenesis of platelet DGs underlie human genetic disorders that cause storage pool disease and manifest with prolonged bleeding. Read More

Gen Thorac Cardiovasc Surg 2017 Aug 9;65(8):478-480. Epub 2016 Nov 9.

Department of General Thoracic Surgery, Dokkyo Medical University, Mibu, Japan.

As the Japanese organ donor allocation system does not permit the allocation of lungs at a priority level to patients on extracorporeal membrane oxygenation (ECMO), many of these patients die before suitable donor lungs become available. We report our first experience with ECMO as a bridge to lung transplantation (LTx) from a brain-dead donor. A 40-year-old man with interstitial lung disease who was listed for LTx 3 years previously, experienced progressive deterioration of respiratory function. Read More

Obstet Med 2016 Dec 5;9(4):171-173. Epub 2016 Aug 5.

Division of Women's and Children's Health, Leeds Teaching Hospitals, NHS Trust, Leeds, UK.

Hermansky-Pudlak syndrome is a rare autosomal recessive disorder estimated to affect 1 in 500,000 to 1,000,000 individuals worldwide. Clinically, it presents as oculocutaneous albinism combined with bleeding diathesis. This is due to the absence of dense bodies in platelets causing a delayed secondary response resulting in prolonged bleeding time despite normal platelet count and coagulation factors. Read More

J AAPOS 2016 Oct 16;20(5):419-424. Epub 2016 Sep 16.

Department of Ophthalmology and Visual Neurosciences, Medical School, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota. Electronic address:

Purpose: Reports of best-corrected visual acuity (BCVA) in albinism are often based on overlapping clinical phenotypes. BCVA in albinism has been shown to improve with age. This study reports a large cross-sectional investigation to determine whether BCVA differs by specific type of albinism when age-corrected. Read More

Mol Genet Metab 2016 Nov 3;119(3):284-287. Epub 2016 Sep 3.

Medical Genetics Branch, NHGRI, NIH, 10 Center Drive, Bethesda, MD 20892-1851, USA. Electronic address:

Purpose: Hemophilia B, an X-linked disease, manifests with recurrent soft tissue bleeding episodes. Hermansky-Pudlak syndrome, a rare autosomal recessive disorder, is characterized by oculocutaneous albinism and an increased tendency to bleed due to a platelet storage pool defect. We report a novel mutation in HPS6 in a Caucasian man with hemophilia B and oculocutaneous albinism. Read More

JCI Insight 2016 Oct 20;1(17):e88947. Epub 2016 Oct 20.

Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.; Department of Veterans Affairs Medical Center, Nashville, Tennessee, USA.

Alveolar epithelial cell (AEC) dysfunction underlies the pathogenesis of pulmonary fibrosis in Hermansky-Pudlak syndrome (HPS) and other genetic syndromes associated with interstitial lung disease; however, mechanisms linking AEC dysfunction and fibrotic remodeling are incompletely understood. Since increased macrophage recruitment precedes pulmonary fibrosis in HPS, we investigated whether crosstalk between AECs and macrophages determines fibrotic susceptibility. We found that AECs from HPS mice produce excessive MCP-1, which was associated with increased macrophages in the lungs of unchallenged HPS mice. Read More

Br J Haematol 2017 Jan 21;176(1):118-123. Epub 2016 Oct 21.

Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.

Hermansky-Pudlak syndrome (HPS) encompasses disorders with abnormal function of lysosomes and lysosome-related organelles, and some patients who develop immunodeficiency. The basic mechanisms contributing to immune dysfunction in HPS are ill-defined. We analysed natural killer (NK) cells from patients diagnosed with HPS-1, HPS-2, HPS-4, and an unreported HPS subtype. Read More

Pigment Cell Melanoma Res 2016 Nov 19;29(6):702-706. Epub 2016 Oct 19.

Center for Medical Genetics, Beijing Childrens Hospital, Capital Medical University, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Beijing, China.

Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by hypopigmentation, bleeding diathesis, and other symptoms due to multiple defects in lysosome-related organelles. Ten HPS subtypes have been identified with mutations in HPS1 to HPS10. Only four patients with HPS-1 have been reported in Chinese population. Read More

Small GTPases 2016 Sep 20:1-8. Epub 2016 Sep 20.

a Institute of Medical Sciences, University of Aberdeen , Foresterhill , Aberdeen , UK.

Our immune system is engaged in a continuous battle against invading pathogens, many of which have evolved to survive in intracellular niches of mammalian hosts. A variety of cellular processes are involved in preventing bacterial invasion or in killing bacteria that successfully invade host cells. Recently, the Rab GTPase Rab32 emerged as critical regulator of a host defense pathway that can eliminate bacterial pathogens. Read More

Arch Pathol Lab Med 2017 Jul 15;141(7):901-915. Epub 2016 Sep 15.

From the Department of Laboratory Medicine & Pathology (Drs Larsen, Smith, and Leslie), Mayo Clinic, Scottsdale, Arizona; the Department of Radiology (Dr Elicker), University of California, San Francisco; Juan Max Boettner Hospital (Drs Fernandez and Arbo-Oze de Morvil), Asunción, Paraguay; and the Department of Medicine (Dr Pereira), Federal University of São Paulo, São Paulo, Brazil.

Context: - Idiopathic pulmonary fibrosis (IPF) is a distinctive clinicopathologic entity and the most common form of progressive diffuse lung scarring in older adults. Idiopathic pulmonary fibrosis manifests histopathologically as the usual interstitial pneumonia pattern. The usual interstitial pneumonia pattern is distinguished by geographically and temporally heterogeneous fibrosis that is peripherally accentuated, often with honeycombing and traction bronchiectasis. Read More

Dev Biol 2017 Jun 3;426(2):472-486. Epub 2016 Sep 3.

Department of Biology, University of Virginia, Charlottesville, VA 22904, USA. Electronic address:

We describe a novel recessive and nonlethal pigmentation mutant in Xenopus tropicalis. The mutant phenotype can be initially observed in tadpoles after stage 39/40, when mutant embryos display markedly reduced pigmentation in the retina and the trunk. By tadpole stage 50 almost all pigmented melanophores have disappeared. Read More

Yi Chuan 2016 Aug;38(8):718-23

Large dense-core vesicles (LDCVs) are characterized as a class of lysosome-related organelles (LROs), which undergo regulated release and play important roles in development, metabolism and homeostasis. The Muted protein is a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), which functions in the biogenesis of lysosomes and LROs. CD63 is a membrane component of lysosomes and LROs. Read More

Ann Am Thorac Soc 2016 Oct;13(10):1839-1846

1 Division of Pulmonary, Critical Care and Sleep Disorders Medicine, Department of Medicine, and Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet dysfunction. More than 50% of cases worldwide are diagnosed on the Caribbean island of Puerto Rico. Genetic testing plays a growing role in diagnosis; however, not all patients with HPS have identified genetic mutations. Read More

Clin Chest Med 2016 09 30;37(3):505-11. Epub 2016 Jun 30.

Division of Pulmonary Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, 2200 Children's Way, Doctor's Office Tower 11215, Nashville, TN 37232, USA; Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Avenue South, B-1220 Medical Center North, Nashville, TN 37232, USA. Electronic address:

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes, including HPS-1, HPS-2, and HPS-4. HPS pulmonary fibrosis shows many of the clinical, radiologic, and histologic features found in idiopathic pulmonary fibrosis, but occurs at a younger age. Despite knowledge of the underlying genetic defects, there are currently no definitive therapeutic or preventive approaches for HPS pulmonary fibrosis other than lung transplant. Read More

J Cell Biol 2016 Aug;214(3):293-308

Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104

Endomembrane organelle maturation requires cargo delivery via fusion with membrane transport intermediates and recycling of fusion factors to their sites of origin. Melanosomes and other lysosome-related organelles obtain cargoes from early endosomes, but the fusion machinery involved and its recycling pathway are unknown. Here, we show that the v-SNARE VAMP7 mediates fusion of melanosomes with tubular transport carriers that also carry the cargo protein TYRP1 and that require BLOC-1 for their formation. Read More

PLoS One 2016 26;11(7):e0159177. Epub 2016 Jul 26.

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

Hermansky-Pudlak Syndrome type-1 (HPS-1) is an autosomal recessive disorder caused by mutations in HPS1 which result in reduced expression of the HPS-1 protein, defective lysosome-related organelle (LRO) transport and absence of platelet delta granules. Patients with HPS-1 exhibit oculocutaneous albinism, colitis, bleeding and pulmonary fibrosis postulated to result from a dysregulated immune response. The effect of the HPS1 mutation on human mast cells (HuMCs) is unknown. Read More

Chronic Illn 2017 Mar 8;13(1):62-72. Epub 2016 Jul 8.

4 HPS Network, Oyster Bay, NY, USA.

Hermansky-Pudlak Syndrome is a rare form of albinism, affecting approximately one in 500,000 to one in 1,000,000 non-Hispanic individuals. The syndrome is more commonly found in Hispanics, where one in 18,00 individuals in Northwestern Puerto Rico are impacted. Because of the rarity of this chronic condition, patients often face challenges in their ability to cope with the diagnosis. Read More

Stem Cell Res 2016 Mar 14;16(2):287-9. Epub 2016 Jan 14.

Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, United States; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, United States; University of Pennsylvania, United States.

Hermansky-Pudlak syndrome type 2 (HPS2) is a rare autosomal recessive disorder resulting from functional mutations in the adaptor-related protein complex 3, beta 1 subunit (AP3B1) gene. This gene plays a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Here we describe the generation of an HPS2 iPS cell line (CHOPHPS2) using a Cre-excisable polycistronic STEMCCA lentivirus. Read More

Stem Cell Res 2016 Mar 14;16(2):233-5. Epub 2016 Jan 14.

Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, United States; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, and University of Pennsylvania, United States.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by deficiencies in lysosome-related organelles such as melanosomes and platelet-dense granules. The disorder is classified into nine different subtypes (HPS1-HPS9) based on genetic mutations in 9 unique genes. Here we describe the generation of an HPS1 iPSC line (CHOPHPS1) using a Cre-excisable polycistronic STEMCCA lentivirus. Read More

Pigment Cell Melanoma Res 2016 Sep 8;29(5):578-82. Epub 2016 Aug 8.

Cell Signaling and Metabolic Disease, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.

Pigmentation in mammals is important for protection of skin and eyes from ultraviolet radiation. Dysregulation of pigmentation is often associated with other conditions that are not directly linked to pigmentation. Here, we isolated spontaneously occurring hypopigmented mice that occasionally experienced severe diarrhea during lactation. Read More

Exp Ther Med 2016 Jun 11;11(6):2247-2253. Epub 2016 Apr 11.

Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China; Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China.

Uniparental disomy (UPD), which is the abnormal situation in which both copies of a chromosomal pair have been inherited from one parent, may cause clinical abnormalities by affecting genomic imprinting or causing autosomal recessive variation. Whole Exome Sequencing (WES) and chromosomal microarray analysis (CMA) are powerful technologies used to search for underlying causal variants. In the present study, WES was used to screen for candidate causal variants in the genome of a Chinese pediatric patient, who had been shown by CMA to have maternal uniparental isodisomy of chromosome 10. Read More

J Hum Genet 2016 Sep 26;61(9):839-42. Epub 2016 May 26.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction and ceroid deposition. We report suspected ocular albinism in two Japanese sisters, caused by mutations in the HPS6 (Hermansky-Pudlak syndrome 6) gene. Trio-based whole-exome sequencing (WES) identified novel compound heterozygous mutations in HPS6 (c. Read More

Blood 2016 Jun 13;127(26):3382-6. Epub 2016 May 13.

Department of Clinical and Experimental Sciences, Institute of Molecular Medicine "Angelo Nocivelli,"

Hermansky-Pudlak syndrome type 2 (HPS2) is a primary immunodeficiency due to adaptor protein-3 (AP-3) complex deficiency. HPS2 patients present neutropenia, partial albinism, and impaired lysosomal vesicles formation in hematopoietic cells. Given the role of dendritic cells (DCs) in the immune response, we studied monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs) in two HPS2 siblings. Read More

Adv Exp Med Biol 2016 ;915:283-94

Institute of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.

Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening bacterial infection that is very common in the developing world. Recent spread of antimicrobial resistant isolates of S. Read More

Cell Cycle 2016 May;15(10):1309-10

a Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments , Paris , France.

J Dermatol 2017 Feb 14;44(2):219-220. Epub 2016 May 14.

Department of Dermatology, Fujita Health University School of Medicine, Toyoake, Japan.

Ophthalmic Genet 2017 Mar-Apr;38(2):194-196. Epub 2016 May 13.

j Department of Pediatric Ophthalmology and Adult Strabismus , Aravind Eye Hospital , Madurai , India.

Ophthalmic Genet 2017 Mar-Apr;38(2):157-160. Epub 2016 Apr 8.

c Department of Surgery , School of Medicine, Medical Sciences Campus, University of Puerto Rico , San Juan , Puerto Rico.

Purpose: To evaluate the benefits of phacoemulsification and intraocular lens implantation in patients with oculocutaneous albinism (OCA).

Method: The charts of 195 patients with OCA who visited a local eye clinic were reviewed. All of these patients had genetic linkage analysis to establish OCA type. Read More

Blood 2016 Apr;127(14):1731

This landmark article by Frantisek Hermansky and Paulus Pudlak, clinicians in Prague, Czechoslovakia, is the first to describe 2 unrelated individuals with what is now called Hermansky-Pudlak syndrome, a bleeding disorder that occurs in association with oculocutaneous albinism. The definition of this syndrome resulted not only in improved care of these patients but also in a functional and molecular understanding of the disease and the role of dense granule secretion in platelet function. Hermansky-Pudlak syndrome is now known to be related to defective dense granule biogenesis due to mutations in any of ≥9 different genes. Read More

J Biol Chem 2016 Apr 23;291(16):8414-27. Epub 2016 Feb 23.

From the Division of Neonatology and

The Hermansky Pudlak syndromes (HPS) constitute a family of disorders characterized by oculocutaneous albinism and bleeding diathesis, often associated with lethal lung fibrosis. HPS results from mutations in genes of membrane trafficking complexes that facilitate delivery of cargo to lysosome-related organelles. Among the affected lysosome-related organelles are lamellar bodies (LB) within alveolar type 2 cells (AT2) in which surfactant components are assembled, modified, and stored. Read More