DOCSLIB.ORG

Urs-Schnyder-Lecture ESPD Dubrovnik Prof Dr. Dr. Judith Fischer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Urs-Schnyder-Lecture ESPD Dubrovnik 02.05.201 Prof Dr. Dr. Judith Fischer University Medical Center Freiburg Institute of Human Genetics Discovery of a gene encoding SLURP-1 in Mal de Meleda Positional cloning 1998 2000 2001 Folie 2 • Milestones • Methods Positional Cloning Homozygosity Mapping Next Generation Sequencing • My Gene identifications - highlights Folie 3 30 years ago… 1990 Department of Dermatology Prof. R. Happle Folie 4 1994 Lutetia = Paris EU-grant: Training and mobility 550km Genetics of psoriasis and genodermatoses Pr. L. Dubertret Dr. C. Blanchet-Bardon Dr. E. Bourrat Folie 5 1996 -1998 • Making tools available • Accelerate elucidation of diseases Genopole Evry • (Gene) Therapy / treatment Dr. J-F. Prud‘homme Dr. J. Weissenbach Dr. S. Saker (DNA bank) Folie 6 Positional Cloning – Reverse Genetics TOOLS MAPS COHORTS TECHNOLOGIES Physical maps DNA Patients Genotyping facilities YACs, BACs Families microsatellite-panels SNP-microarrays Genetic maps Linkage studies Bioinformatics, Statistics Microsatellites /SNPs Homozygosity Linkage (LOD scores) Human genome project mapping Association studies (p- HapMap (consanguineous) values) GWAS 1000 genome project Sequencing facilities Positional Cloning Using maps, cohorts and technologies 2001 First draft of Human genome sequence Gene1 Gene2 From: The general approach to positional cloning Folie 8 1998-2010 Genopole - Evry Gene identification • Positional cloning (< 2006) • Next Generation Sequencing NGS (> 2006) Whole Exome Sequencing Pr. M. Lathrop Pr. J. Weissenbach Folie 9 COHORTS DNA from > 1.000 families with genodermatoses CNG/Généthon: France Algeria Tunisia Morocco Turkey Italy Portugal UK Colombie Sub-Sahara Afrique Syria Spain Lebanon Geneskin EU Sweden Danmark Switzerland Italy Active Participation day and night in the Algerian desert 11 HOMOZYGOSITY MAPPING * I. A chromosomal region which 2 1 3 4 contains the segregating allele from a same ancestor is transmitted via both sides of II. * * the family Search for common 7 8 1 3 4 1 * homozygosity regions in * 5 6 affected children in consanguineous families III. 71 15 Strategy 3 times more powerful for localizing a gene * * * * Opportunity to localize genes IV. for very rare diseases 7 1 7 5 1 1 1 5 Discovery of a gene encoding SLURP-1 in Mal de Meleda Positional cloning 1998 2000 2001 Folie 13 Positional cloning of Mal de Meleda Family cohorts: Consanguineous families with Mal de Melda from Algeria Pr. B. Bouadjar Bouadjar B, Benmazouzia S, Prud'homme J, Cure S, Fischer J. Clinical and Genetic Studies of 3 Large, Consanguineous, Algerian Families With Mal de Meleda. Arch Dermatol. 2000;136(10):1247–1252. doi:10.1001/archderm.136.10.1247 Folie 14 Positional cloning of Mal de Meleda Family cohorts: Consanguineous families with Mal de Melda from Algeria Bouadjar B, Benmazouzia S, Prud'homme J, Cure S, Fischer J. Clinical and Genetic Studies of 3 Large, Consanguineous, Algerian Families With Mal de Meleda. Arch Dermatol. 2000;136(10):1247–1252. doi:10.1001/archderm.136.10.1247 Folie 15 Genetic linkage of Meleda disease to chromosome 8qter Fischer et al. (1998) Homozygosity mapping Fischer et al. (1998) Genetic linkage of Meleda disease to chromosome 8qter. Eur J Hum Genet Bouadjar et al. (2000) Clinical and Genetic Studies of 3 Large, Consanguineous, Algerian Families With Mal de Meleda Arch Dermatol. Folie 16 Genetic linkage of Meleda disease to chromosome 8qter Fischer et al. (1998) Folie 17 Mutations in the gene encoding SLURP-1 in Mal de Meleda Fischer et al. (2001) Hum Mol Genet Patient 1.9 1.11 1.6 2.12 3.19 6.12 7.10 9.5 10.10 11.4 12.9 14.3 16.3 17.3 18.15 4.17 5.9 8.10 13.3 15.6 19.3 Origin A A A A A A A A A A A C C C C A A A C C C Marker D8S1717 3 6 6 11 9 9 3 9 9 9 9 9 3 3 6 6 3 3 9 9 6 6 1 8 3 9 3 9 9 9 9 4 12 12 11 11 3 3 3 3 3 3 D8S1704 5 2 2 3 5 3 3 3 3 3 3 3 5 5 2 2 3 5 3 3 2 2 1 3 1 3 5 3 3 3 3 2 1 1 2 2 1 1 1 1 1 4 CNG001 7 3 3 4 4 5 11 5 7 7 5 5 2 2 3 3 5 2 5 5 3 3 4 6 4 6 1 5 6 6 2 5 6 6 4 4 4 4 4 4 4 8 D8S1727 3 4 - - 3 3 3 3 3 3 3 3 6 6 4 4 6 6 3 3 4 4 - - - - - - - - 8 8 3 3 - - 8 8 8 8 8 8 CNG002 4 2 2 1 2 2 2 2 4 4 2 2 2 2 2 2 2 2 2 2 2 2 2 3 1 1 3 2 1 1 2 2 2 2 3 3 2 2 2 2 2 3 CNG003 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 7 7 7 7 7 7 8 8 8 8 8 8 D8S1751 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 1 1 1 1 1 1 1 1 1 1 1 1 D8S1836 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 5 5 5 5 5 5 4 4 4 4 4 4 CNG004 7 7 7 7 8 11 5 5 9 9 11 11 6 6 7 7 6 6 11 11 4 4 6 6 6 6 6 6 6 6 9 9 7 9 9 9 6 6 6 6 6 6 CNG005 4 4 2 4 4 4 2 2 4 4 4 4 4 4 4 4 4 4 1 4 2 2 2 2 2 2 2 2 2 2 4 4 2 4 4 4 2 2 2 4 2 2 D8S2334 9 9 7 9 7 3 7 7 7 3 3 3 1 1 9 9 2 2 4 3 5 5 9 9 9 9 9 9 9 9 1 1 9 1 2 2 9 9 9 3 9 8 D8S1926 2 2 4 2 5 4 2 2 3 4 4 4 5 5 2 2 5 5 4 4 2 2 2 2 2 2 2 2 2 2 2 2 4 2 2 2 1 1 1 5 1 2 D8S1925 4 4 4 4 1 4 5 5 6 7 4 4 6 6 4 4 6 6 3 4 6 6 6 6 6 6 6 6 6 6 6 6 7 4 6 6 6 6 6 4 6 6 Mutation 82delT Altered Splicing C286T C28 32X 178+1g a R96X • 19 families, all patients with a homozygous haplotype on 8qter • Smallest segregating interval 1 cM (recombination events, loss of homozygosity) • Contained only 3 genes • Maximum LOD score 24.19 for marker CNG003 at θ = 0.0. • 3 different haplotpes – 3 different mutations in gene ARS (component B) • ARS (component B) : 3 exons, 103 amino acids • coding for SLURP-1 Folie 18 International cooperations 2002 - Dubrovnik, Zagreb, Evry, Lausanne, Edinburgh and Netherlands Folie 19 Marakchi et al., 2003 JID Large consanguineous pedigrees - Sfax Tunisia Folie 20 New mutations – 5 Haplotypes – Sfax Tunisia Marakchi et al., 2003 JID Folie 21 Slurping across the mare nostrum Commentary to Marrakchi et al. JID 2003, 120:351-355 Folie 22 Functional studies : group of Daniel Hohl Folie 23 Mapping/Localization Papillon-Lefevre-Syndrom 1997 1997 2001 1999, two different groups (Hart et al., Toomes et al.) reported first PLS to be due to mutations in the gene encoding cathepsin C, a lysosomal cysteine protease of the papain type also known as dipeptidyl aminopeptidase (CTSC and DPP1) Folie 24 Ichthyoses Autosomal Recessive Congenital Ichthyoses ARCIs Folie 25 Two new loci for autosomal recessive ichthyosis on Chromosomes 3p21 and 19p12-q12 and evidence for Further Genetic Heterogeneity (Fischer et al.) Positional cloning in 51 consanguineous families without TGM1 mutations 12 families linked to 2 new loci Chrom. Chrom. 3q21 19p12-19q12 2000 Folie 26 Locus on chrom. 3p21 : Syndromic ichthyosis Chanarin-Dorfman-Syndrom Neutral lipd storage syndrome with Ichthyosis NLSDI 2001 Folie 27 Jordan’s Chanarin- anomalies in Dorfman polynuclear granulocytes Syndrome NLSDI liver and muscle enzymes Two new mutations of the ABHD5 gene in a new adult case of Chanarin Dorfman syndrome: an uncommon lipid storage disease. Schleinitz et al 2005, Arch Dermatol. HES Muscle biopsy atrophic (Sudan black) muscle EM skin biopsy EM muscle HES skin biopsy with vacuoles in keratinocytes Some families with typical Jordans anomalies had NO MUTATIONS in CGI58/ABDH5 (?? *) Peripheral blood smear showing lipid vacuoles (arrows) in neutrophils (Jordans anomaly). Similar lipid deposition was also observed in hepatocyte nuclei. (Ciesek et al., 2006) Folie 29 *2007 PNPLA2 = ATGL = Adipos triglyceride lipase Folie 30 Mutations of ATGL/PNPLA2 in Neutral lipid storage disease with myopathy NLSDM Fischer et al., 2007 Mutations of ATGL/PNPLA2 in Neutral lipid storage disease with myopathy NLSDM Fischer et al., 2007 Comparaison of phenotypes, metabolic and biochemical defect between patients with NLSDM and CDS/NLSDI RT-PCR Accumulation of lipids in muscle and skin NLSDM Locus on 19p12-19q12 2006 Folie 34 Positional cloning of lamellar ichthyosis type 3 LI3 Fischer et al., 2000 6 consanguineous families Genome-wide scan with microsatellites →Search for common homozygosity regions 5.9 cM in affected children (Homozygosity mapping) Gene Localisation of LI3 on chromosome 19p21-q21 (Fischer et al 2000) Initial smallest common interval 5.9 cM 1cM ~1Mb 12 consanguineous families linked to chrom.
Recommended publications
  • Keratosis Circumscripta Revisited: a Case Report and Review of the Literature

    Keratosis Circumscripta Revisited: a Case Report and Review of the Literature

    CONTINUING MEDICAL EDUCATION Keratosis Circumscripta Revisited: A Case Report and Review of the Literature LCDR Eric P. Brumwell, MC, USN; LCDR Sean J. Murphy, MC, USN GOAL To understand keratosis circumscripta to better manage patients with the condition OBJECTIVES Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Describe the clinical presentation of keratosis circumscripta. 2. Discuss the disorders often compared to keratosis circumscripta. 3. Identify treatment options for keratosis circumscripta. CME Test on page 378. This article has been peer reviewed and approved Einstein College of Medicine is accredited by by Michael Fisher, MD, Professor of Medicine, the ACCME to provide continuing medical edu- Albert Einstein College of Medicine. Review date: cation for physicians. April 2007. Albert Einstein College of Medicine designates This activity has been planned and imple- this educational activity for a maximum of 1 AMA mented in accordance with the Essential Areas PRA Category 1 CreditTM. Physicians should only and Policies of the Accreditation Council for claim credit commensurate with the extent of their Continuing Medical Education through the participation in the activity. joint sponsorship of Albert Einstein College of This activity has been planned and produced in Medicine and Quadrant HealthCom, Inc. Albert accordance with ACCME Essentials. Drs. Brumwell and Murphy report no conflict of interest. The authors report no discussion of off-label use. Dr. Fisher reports no conflict of interest. Keratosis circumscripta, also known as psoriasis been shown to improve, but not resolve, with kerat- circumscripta with palmoplantar keratosis, is a inolytic therapies. Some debate exists concern- rarely reported condition that manifests as well- ing the terminology used to identify this condition.
  • Mal De Meleda in a Taiwanese

    Mal De Meleda in a Taiwanese

    S.C. Chao, F.J. Lai, M.H. Yang, et al MAL DE MELEDA IN A TAIWANESE Sheau-Chiou Chao, Feng-Jei Lai, Mei-Hui Yang, and Julia Yu-Yun Lee Abstract: Mal de Meleda (MDM) is a rare form of recessive transgressive palmoplantar erythrokeratoderma for which mutations in the ARS gene have been identified recently. The ARS gene encodes SLURP-1, a secreted epidermal neuromodulator involved in epidermal homeostasis and inhibition of tumor necrosis factor-α release. A 27-year- old Taiwanese woman who had a history of palmoplantar keratoderma since birth presented with severe erythrokeratoderma of the hands and feet in a glove-and-stocking distribution with conical tapering of the fingers, and involvement of the skin over the major joints and thighs. There were also widespread mottled hyperpigmented macules. Mutation analysis revealed a homozygous missense mutation (G86R) in exon 3 of ARS gene of this patient. Key words: ARS protein, human; Keratoderma, palmoplantar; Mutation, missense; Neuronal nicotinic acetylcholine receptor alpha7; Taiwan J Formos Med Assoc 2005;104:276-8 Keratoderma palmoplantare transgrediens or mal de that appeared soon after birth. The family reported no Meleda (MDM) is a rare autosomal recessive inflam- known consanguinity. She was the only affected member matory keratoderma, characterized by diffuse erythema in the family. On examination, the patient had marked and hyperkeratosis of the hands and feet that appears erythema and hyperkeratosis of the hands and feet soon after birth and progressively extends to the dorsal in a glove-and-stocking distribution, accompanied by aspect of the hands and feet and around the wrist malodor (Fig.).
  • Transport Development Strategy of the Republic of Croatia (2017 – 2030)

    Transport Development Strategy of the Republic of Croatia (2017 – 2030)

    Transport Development Strategy of the Republic of Croatia (2017 – 2030) Republic of Croatia MINISTRY OF THE SEA, TRANSPORT AND INFRASTRUCTURE Transport Development Strategy of the Republic of Croatia (2017 - 2030) 2nd Draft April 2017 The project is co-financed by the European Union from the European Regional Development Fund. Republic of Croatia Ministry of the Sea, Transport and Infrastructure I Transport Development Strategy of the Republic of Croatia (2017 – 2030) TABLE OF CONTENTS 1 Introduction ............................................................................................................. 1 1.1 Background on development of a Croatian Comprehensive National Transport Plan .................................................. 1 1.2 Objectives of the Transport Development Strategy (TDS 2016) ............................. 4 1.3 Revision of the TDS (2016) Ex-Ante conditionality .................................................. 4 1.4 Methodology for the development of the TDS (2016) ............................................ 5 2 Analysis .................................................................................................................... 7 2.1 General aspects of transport ................................................................................... 7 2.2 Public transport and zero-emission modes ........................................................... 34 2.3 Rail Transport......................................................................................................... 72 2.4 Road transport
  • Route Evaluation Report Croatia Eurovelo 8 – Mediterranean Route

    Route Evaluation Report Croatia Eurovelo 8 – Mediterranean Route

    Route Evaluation Report Croatia EuroVelo 8 – Mediterranean Route MEDCYCLETOUR Project Davorin Belamarić April 27th 2018 Contents 1 Background ......................................................................................................................... 5 1.1 Mission of the project and report objectives ................................................................. 5 1.2 Organization ................................................................................................................ 7 1.3 Brief methodological explanations ................................................................................ 8 1.3.1 Different phases of the route evaluation ................................................................ 8 1.3.2 ECS – European Certification Standard used for this evaluation ........................... 9 1.3.3 Used tools and equipment, photographs ..............................................................10 1.4 Overview of the sections .............................................................................................10 2 Infrastructure ......................................................................................................................16 2.1 Existing route infrastructure ........................................................................................16 2.1.1 Public transport ....................................................................................................19 2.2 Critical deficiencies .....................................................................................................30
  • WES Gene Package Multiple Congenital Anomalie.Xlsx

    WES Gene Package Multiple Congenital Anomalie.Xlsx

    Whole Exome Sequencing Gene package Multiple congenital anomalie, version 5, 1‐2‐2018 Technical information DNA was enriched using Agilent SureSelect Clinical Research Exome V2 capture and paired‐end sequenced on the Illumina platform (outsourced). The aim is to obtain 8.1 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA‐MEM algorithm (reference: http://bio‐bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x A4GALT [Blood group, P1Pk system, P(2) phenotype], 111400 607922 101 100 100 99 [Blood group, P1Pk system, p phenotype], 111400 NOR polyagglutination syndrome, 111400 AAAS Achalasia‐addisonianism‐alacrimia syndrome, 231550 605378 73 100 100 100 AAGAB Keratoderma, palmoplantar,
  • Dubrovnik, Croatia 2019 TABLE of CONTENTS

    Dubrovnik, Croatia 2019 TABLE of CONTENTS

    GLOBAL SUSTAINABLE TOURISM COUNCIL DESTINATION ASSESSMENT Dubrovnik, Croatia 2019 TABLE OF CONTENTS Executive Summary.......................................................................................................................................................................1 Acknowledgements.......................................................................................................................................................................4 Acronyms........................................................................................................................................................................................... 5 List of Tables.....................................................................................................................................................................................6 List of Figures...................................................................................................................................................................................7 Introduction.......................................................................................................................................................................................8 Overview of Tourism in Dubrovnik ......................................................................................................................................11 A. Geography and Tourism Statistics..................................................................................................................11
  • Croatia National Report 2007

    Croatia National Report 2007

    CROATIA NATIONAL REPORT 2007 I Network The total length of motorway network, as completed by the end of 2007 in Croatia, amounts to 1163.5 km. In 2007, 75,9 km of new motorways and 3,8 km of semi motorways were built (as compared to 43 km that were built in 2006), and 15,7 km of existing roads were upgraded to the full motorway profile: On the Motorway A1: Zagreb - Split - Ploče; Dugopolje-Bisko-Šestanovac Sections (37 km) - opened to traffic in full profile in 06/2007 On the Motorway A2: Zagreb - Macelj Krapina-Macelj Section (17.2 km) –13,4 km was completed as full motorway and 3,8 km as semi motorway On the Motorway A5: Beli Manastir-Osijek-border with Bosnia and Herzegovina Sredanci-Đakovo Section (23 km) – opened to traffic as full motorway in 11/2007 On the Motorway A6: Zagreb - Rijeka - on the Vrbovsko-Bosiljevo Section (8,44 km) – upgrade to the full motorway profile of the viaduct Zeceve Drage, tunnel Veliki Gložac, viaduct Osojnik and viaduct Severinske Drage together with corresponding motorway segments in 06/2007 - on the Oštrovica-Kikovica Section (7,25 km) - upgrade to the full motorway profile in 11/2007 On the Motorway A11: Zagreb – Sisak On the Jakuševec-Velika Gorica South Section – completion of the interchange Velika Gorica South and 2,5 km of a motorway segment in 5/2007 and in 09/2007 In Croatia, motorways are operated by 4 companies, i.e. by Hrvatske autoceste d.o.o. (operates all toll motorways except for those in concession) and by three concession companies BINA-ISTRA d.d.
  • The First Reported Case of a Variant of Mal De Maleda of the Gamborg

    The First Reported Case of a Variant of Mal De Maleda of the Gamborg

    Our Dermatology Online Case Report Th e fi rrstst rreportedeported ccasease ooff a vvariantariant ooff MMalal ddee MMaledaaleda ooff tthehe GGamborg-Nielsenamborg-Nielsen ttypeype iinn aann EEgyptiangyptian ooriginrigin ppatientatient Khalid M. Al-Husain1, Ahmed A. Al-Thubaiti1, Farah M. Alzahrani2, Iqbal A. Bukhari3, Mohammad El-Shawarby4 1College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Kingdom of Saudi Arabia, 2College of Medicine, Arabian Gulf University (AGU), Bahrain, 3Dermatology Department, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU) and King Fahd Hospital of the University, Dammam, Kingdom of Saudi Arabia, 4Pathology Department, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU) and King Fahd Hospital of the University, Dammam, Kingdom of Saudi Arabia Corresponding author: Prof. Iqbal A. Bukhari, E-mail: [email protected] ABSTRACT Mal de Meleda is a rare genodermatosis with an autosomal recessive inheritance. Mutations in the SLURP1 gene are the cause of this disease. Clinically, it is characterized by progressive palmoplantar hyperkeratosis exhibiting a transgradiens pattern extending to the dorsal aspects of the hands and feet in a glove and stocking pattern. It is also associated with hyperhidrosis, nail changes, subungual hyperkeratosis and perioral erythema. Here we report the first case of Gamborg-Nielsen variant of Mal de Meleda disorder in a patient of an Egyptian origin. Key words: Mal de Meleda; Keratoderma; Genodermatosis; SLURP1 gene INTRODUCTION in
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0210567 A1 Bevec (43) Pub

    (12) Patent Application Publication (10) Pub. No.: US 2010/0210567 A1 Bevec (43) Pub

    US 2010O2.10567A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0210567 A1 Bevec (43) Pub. Date: Aug. 19, 2010 (54) USE OF ATUFTSINASATHERAPEUTIC Publication Classification AGENT (51) Int. Cl. A638/07 (2006.01) (76) Inventor: Dorian Bevec, Germering (DE) C07K 5/103 (2006.01) A6IP35/00 (2006.01) Correspondence Address: A6IPL/I6 (2006.01) WINSTEAD PC A6IP3L/20 (2006.01) i. 2O1 US (52) U.S. Cl. ........................................... 514/18: 530/330 9 (US) (57) ABSTRACT (21) Appl. No.: 12/677,311 The present invention is directed to the use of the peptide compound Thr-Lys-Pro-Arg-OH as a therapeutic agent for (22) PCT Filed: Sep. 9, 2008 the prophylaxis and/or treatment of cancer, autoimmune dis eases, fibrotic diseases, inflammatory diseases, neurodegen (86). PCT No.: PCT/EP2008/007470 erative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the S371 (c)(1), present invention relates to pharmaceutical compositions (2), (4) Date: Mar. 10, 2010 preferably inform of a lyophilisate or liquid buffersolution or artificial mother milk formulation or mother milk substitute (30) Foreign Application Priority Data containing the peptide Thr-Lys-Pro-Arg-OH optionally together with at least one pharmaceutically acceptable car Sep. 11, 2007 (EP) .................................. O7017754.8 rier, cryoprotectant, lyoprotectant, excipient and/or diluent. US 2010/0210567 A1 Aug. 19, 2010 USE OF ATUFTSNASATHERAPEUTIC ment of Hepatitis BVirus infection, diseases caused by Hepa AGENT titis B Virus infection, acute hepatitis, chronic hepatitis, full minant liver failure, liver cirrhosis, cancer associated with Hepatitis B Virus infection. 0001. The present invention is directed to the use of the Cancer, Tumors, Proliferative Diseases, Malignancies and peptide compound Thr-Lys-Pro-Arg-OH (Tuftsin) as a thera their Metastases peutic agent for the prophylaxis and/or treatment of cancer, 0008.
  • CROATIA LOCAL SINGLE SKY IMPLEMENTATION Level2020 1 - Implementation Overview

    CROATIA LOCAL SINGLE SKY IMPLEMENTATION Level2020 1 - Implementation Overview

    LSSIP 2020 - CROATIA LOCAL SINGLE SKY IMPLEMENTATION Level2020 1 - Implementation Overview Document Title LSSIP Year 2020 for Croatia Info Centre Reference 20/12/22/56 Date of Edition 15/03/2021 LSSIP Focal Point T. Plavčić – DGCA CROATIA - [email protected] LSSIP Contact Person Véronique MARTOU - EUROCONTROL / NMD/INF/PAS [email protected] LSSIP Support Team [email protected] Status Released Intended for EUROCONTROL Stakeholders Available in https://www.eurocontrol.int/service/local-single-sky-implementation- monitoring Reference Documents LSSIP Documents https://www.eurocontrol.int/service/local-single-sky-implementation- monitoring Master Plan Level 3 – Plan https://www.eurocontrol.int/publication/european-atm-master-plan- Edition 2020 implementation-plan-level-3 Master Plan Level 3 – Report https://www.eurocontrol.int/publication/european-atm-master-plan- Year 2020 implementation-report-level-3 European ATM Portal https://www.atmmasterplan.eu/ STATFOR Forecasts https://www.eurocontrol.int/statfor National AIP http://www.crocontrol.hr/UserDocsImages/AIS%20produkti/eAIP/start.html FAB Performance Plan covering Latest FABCE Performance Plan V2.0 RP2 – 2014-2019 For details contact: Mr Matej Eljon: [email protected] LSSIP Year 2020 Croatia Released Issue APPROVAL SHEET The following authorities have approved all parts of the LSSIP Year 2020 document and the signatures confirm the correctness of the reported information and reflect the commitment to implement the actions laid down in the European ATM Master Plan Level 3 (Implementation View) – Edition 2020. Stakeholder / Name Position Signature and date Organisation Ministry of the Sea, Transport and Tomislav Mihotić State Secretary Infrastructure Croatian Civil Aviation Marin Puh Director Agency Coatia Control Ltd.
  • Palmoplantar Keratoderma of the Gamborg-Nielsen Type Is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal De Meleda

    Palmoplantar Keratoderma of the Gamborg-Nielsen Type Is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal De Meleda

    Acta Derm Venereol 2014; 94: 707–710 CLINICAL REPORT Palmoplantar Keratoderma of the Gamborg-Nielsen Type is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal de Meleda Linshu ZHAO1, Anders VAHLQUIST2*, Marie VIRtanen2, Lena WENNERSTRAND3, Lisbet K. LIND3, Anita LUNDSTRÖM4 and Maritta HELLSTRÖM PIGG1 Departments of 1Immunology, Genetics and Pathology and 2Medical Sciences, Uppsala University, Uppsala, and 3Departments of Medical Biosciences, Medical and Clinical Genetics and 4Public Health and Clinical Medicine, Umeå University, Umeå, Sweden Palmoplantar keratoderma of the Gamborg-Nielsen also observed. Mal de Meleda (MDM; OMIM 248300) type (PPK-GN) is a rare autosomal recessive skin disor- or keratosis palmoplantaris transgradiens of Siemens der described in patients from Sweden. Mal de Meleda is an autosomal recessive skin disorder first described (MDM) is also a rare autosomal recessive inherited PPK in 1898 by Neumann (2) in patients from the island of first reported in 5 families from the island of Meleda. Mljet (Meleda) in Dalmatia, Croatia. MDM is clinically The 2 conditions phenotypically overlap and are charac- characterised by symmetric transgressive PPK, and so- terised by palmoplantar erythematous hyperkeratotic metimes associated with lichenoid or keratotic plaques plaques. The genetic background giving rise to PPK-GN over joints, redness in the palms and soles, brachydactyly, has hitherto been unknown, whereas MDM is known to cone-shaped fingers, pseudoainhum and nail abnorma- be caused by mutations in the gene encoding secreted lities with pachyonychia. The progressive lesions can Ly-6/uPAR-related protein 1, SLURP-1. In the present lead to reduced mobility of hands and feet because of study we scrutinised individuals affected by PPK-GN for contractions (2–8).
  • Towards a Comprehensive Resource for Elucidating the Pathogenesis of Inherited Keratodermas

    Towards a Comprehensive Resource for Elucidating the Pathogenesis of Inherited Keratodermas

    Towards a Comprehensive Resource for Elucidating the Pathogenesis of Inherited Keratodermas Dr Mozheh Zamiri BSc (Hons), MB ChB, MRCP Doctorate of Medicine University of Edinburgh 2009 Alan Lyell Centre for Dermatology, Glasgow & Section of Dermatology, University of Glasgow ABSTRACT Keratoderma – pathological hyperkeratosis of palms and soles - is a cause of disability in many clinical situations, including the rare and heterogeneous group of inherited palmoplantar keratodermas (PPKs). The aim of this study was to work towards better understanding of molecular mechanisms active in the pathogenesis of PPK by the creation of a cell and tissue culture resource and its initial application to laboratory studies. My study was based on a diverse group of autosomal dominant disorders, previously ascertained in families from Scotland, in whom the precise genetic aetiology was known. I established a tissue and cell culture resource of inherited keratodermas of known single-gene aetiology from patients with proven keratin 1, 9, 17, loricrin and mitochondrial mutations. An additional pedigree with striate keratoderma with an unknown mutation was recruited, and the causative mutation identified as a novel heterozygous A-to-T transversion in exon 5 (c.430A>T) of the desmoglein 1 gene, converting an arginine residue to a premature termination codon (p.Arg144stop). The keratinocyte culture resource was established from patients with keratin 1, 9, 17 and loricrin mutations, as well as controls. Due to the pain associated with direct infiltration of plantar skin, biopsies were obtained using peripheral nerve block for plantar biopsy. The effectiveness of this approach, which may be useful for future administration of treatment, was made the subject of an open clinical trial.