88,348 results match your criteria Hereditary Angioedema


[The multifaceted concept of mental disorder].

Authors:
Heinz Häfner

Fortschr Neurol Psychiatr 2018 Dec 17. Epub 2018 Dec 17.

Zentralinstitut für Seelische Gesundheit, AG Schizophrenieforschung; Medizinische Fakultät Mannheim / Universität Heidelberg.

The concept of mental disorder has many facets. Specific concepts of disease or disorder stand for individual entities, classified as diagnoses. Ideally, they are based on discrete physical, neurobiological or - as is the case with hereditary diseases - genetic findings. Read More

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December 2018

Prevalence of Germline Mutations in Polyposis and Colorectal Cancer-associated Genes in Patients With Multiple Colorectal Polyps.

Clin Gastroenterol Hepatol 2018 Dec 14. Epub 2018 Dec 14.

Ambry Genetics, Aliso Viejo, CA.

Background And Aims: Guidelines recommend genetic testing of patients with 10 or more cumulative adenomatous polyps. However, little is known about the utility of these tests-especially for older patients. We aimed to determine the prevalence of pathogenic mutations in patients with multiple colorectal polyps, stratified by age. Read More

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December 2018

R125H, W240S, C386R, and V507I SLC4A11 mutations associated with corneal endothelial dystrophy affect the transporter function but not trafficking in PS120 cells.

Exp Eye Res 2018 Dec 14. Epub 2018 Dec 14.

School of Optometry, Indiana University Bloomington, Bloomington, IN, USA. Electronic address:

SLC4A11 mutations are associated with Fuchs' endothelial corneal dystrophy (FECD), congenital hereditary endothelial dystrophy (CHED) and Harboyan syndrome (endothelial dystrophy with auditory deficiency). Mice with genetically ablated Slc4a11 recapitulate CHED, exhibiting significant corneal edema and altered endothelial morphology. We recently demonstrated that SLC4A11 functions as an NH sensitive, electrogenic H transporter. Read More

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December 2018
3 Reads

Engineered zinc-finger nuclease to generate site-directed modification in the KLF1 gene for fetal hemoglobin induction.

J Cell Biochem 2018 Dec 16. Epub 2018 Dec 16.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Elevation of hemoglobin F (HbF) ameliorates symptoms of β-thalassemia, as a common autosomal recessive disorder. In this study, the ability of an engineered zinc-finger nuclease (ZFN) system was assesed to disrupt the KLF1 gene to inhibit the γ to β hemoglobin switching in K562 cells. This study was performed using a second generation integration-deficient lentiviral vector assigned to transient gene targeting. Read More

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December 2018

Keeping ribosomal DNA intact: a repeating challenge.

Chromosome Res 2018 Dec 17. Epub 2018 Dec 17.

Section of Oncogenetics, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, de Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.

More than half of the human genome consists of repetitive sequences, with the ribosomal DNA (rDNA) representing two of the largest repeats. Repetitive rDNA sequences may form a threat to genomic integrity and cellular homeostasis due to the challenging aspects of their transcription, replication, and repair. Predisposition to cancer, premature aging, and neurological impairment in ataxia-telangiectasia and Bloom syndrome, for instance, coincide with increased cellular rDNA repeat instability. Read More

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December 2018

Vitamin D-Resistant Rickets and Cinacalcet-One More Favorable Experience.

Front Pediatr 2018 28;6:376. Epub 2018 Nov 28.

Department of Clinical Chemistry, University Hospital Center of Liège, University of Liège, Liège, Belgium.

Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by early onset of severe rickets, with a complete triad of clinical, biochemical and skeletal abnormalities. Homozygous or heterozygous mutations in the vitamin D receptor () gene leading to complete or partial target organ resistance to the action of 1α, 25-dihydroxyvitamin D3 (the active form of vitamin D) are responsible for HVDRR. Theoretically the therapeutic goal is to overcome this tissue resistance, and to normalize calcium and phosphate homeostasis. Read More

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November 2018

Pregnancy unmasking symptoms of undiagnosed lymphangioleiomyomatosis: Case report and review of literature.

Respir Med Case Rep 2019 23;26:63-67. Epub 2018 Nov 23.

Centegra Health Care System, USA.

Cystic lung diseases are a group of disorders that appear similar on radiological studies on chest computed tomography. Each disorder is characterized by its own etiology, pathophysiology, course of progression and manifestation. Lymphangioleiomyomatosis (LAM) is one of the cystic lung diseases that can either be hereditary or sporadic. Read More

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November 2018

Minimally Invasive Total Hip Arthroplasty in a Patient with Hereditary Multiple Exostoses: A Case Report.

Malays Orthop J 2018 Nov;12(3):53-56

Center for Joint Disease, Chonnam National University Hwasun Hospital, Jeonnam, Republic of Korea.

Hip geometry abnormalities found in patients with hereditary multiple exostoses (HME) could promote premature hip joint degeneration which needs treatment. We report the case of a 45-year old male with right hip arthrosis who underwent two-incision minimally invasive (MIS-2) total hip arthroplasty (THA), with satisfactory outcome. This technique could be an alternative approach for performing THA in patients with hereditary multiple exostoses. Read More

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November 2018

Novel c.C2254T (p.Q752*) mutation in (SPG15) gene in a patient with hereditary spastic paraparesis.

J Genet 2018 Dec;97(5):1469-1472

Oasi Research Institute-IRCCS, Troina 94018, Italy.

Hereditary spastic paraplegias are clinically and genetically heterogeneous degenerative disorders, and pathological variants in the autosomal recessive gene are considered as very rare causes. We describe a novel mutation in gene found in a patient with autosomal recessive spastic paraplegias. The use of a 'target-gene' approach allowed us to expand the clinical spectrum associated with hereditary spastic paraplegias. Read More

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December 2018

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Authors:
Nasim Mavaddat Kyriaki Michailidou Joe Dennis Michael Lush Laura Fachal Andrew Lee Jonathan P Tyrer Ting-Huei Chen Qin Wang Manjeet K Bolla Xin Yang Muriel A Adank Thomas Ahearn Kristiina Aittomäki Jamie Allen Irene L Andrulis Hoda Anton-Culver Natalia N Antonenkova Volker Arndt Kristan J Aronson Paul L Auer Päivi Auvinen Myrto Barrdahl Laura E Beane Freeman Matthias W Beckmann Sabine Behrens Javier Benitez Marina Bermisheva Leslie Bernstein Carl Blomqvist Natalia V Bogdanova Stig E Bojesen Bernardo Bonanni Anne-Lise Børresen-Dale Hiltrud Brauch Michael Bremer Hermann Brenner Adam Brentnall Ian W Brock Angela Brooks-Wilson Sara Y Brucker Thomas Brüning Barbara Burwinkel Daniele Campa Brian D Carter Jose E Castelao Stephen J Chanock Rowan Chlebowski Hans Christiansen Christine L Clarke J Margriet Collée Emilie Cordina-Duverger Sten Cornelissen Fergus J Couch Angela Cox Simon S Cross Kamila Czene Mary B Daly Peter Devilee Thilo Dörk Isabel Dos-Santos-Silva Martine Dumont Lorraine Durcan Miriam Dwek Diana M Eccles Arif B Ekici A Heather Eliassen Carolina Ellberg Christoph Engel Mikael Eriksson D Gareth Evans Peter A Fasching Jonine Figueroa Olivia Fletcher Henrik Flyger Asta Försti Lin Fritschi Marike Gabrielson Manuela Gago-Dominguez Susan M Gapstur José A García-Sáenz Mia M Gaudet Vassilios Georgoulias Graham G Giles Irina R Gilyazova Gord Glendon Mark S Goldberg David E Goldgar Anna González-Neira Grethe I Grenaker Alnæs Mervi Grip Jacek Gronwald Anne Grundy Pascal Guénel Lothar Haeberle Eric Hahnen Christopher A Haiman Niclas Håkansson Ute Hamann Susan E Hankinson Elaine F Harkness Steven N Hart Wei He Alexander Hein Jane Heyworth Peter Hillemanns Antoinette Hollestelle Maartje J Hooning Robert N Hoover John L Hopper Anthony Howell Guanmengqian Huang Keith Humphreys David J Hunter Milena Jakimovska Anna Jakubowska Wolfgang Janni Esther M John Nichola Johnson Michael E Jones Arja Jukkola-Vuorinen Audrey Jung Rudolf Kaaks Katarzyna Kaczmarek Vesa Kataja Renske Keeman Michael J Kerin Elza Khusnutdinova Johanna I Kiiski Julia A Knight Yon-Dschun Ko Veli-Matti Kosma Stella Koutros Vessela N Kristensen Ute Krüger Tabea Kühl Diether Lambrechts Loic Le Marchand Eunjung Lee Flavio Lejbkowicz Jenna Lilyquist Annika Lindblom Sara Lindström Jolanta Lissowska Wing-Yee Lo Sibylle Loibl Jirong Long Jan Lubiński Michael P Lux Robert J MacInnis Tom Maishman Enes Makalic Ivana Maleva Kostovska Arto Mannermaa Siranoush Manoukian Sara Margolin John W M Martens Maria Elena Martinez Dimitrios Mavroudis Catriona McLean Alfons Meindl Usha Menon Pooja Middha Nicola Miller Fernando Moreno Anna Marie Mulligan Claire Mulot Victor M Muñoz-Garzon Susan L Neuhausen Heli Nevanlinna Patrick Neven William G Newman Sune F Nielsen Børge G Nordestgaard Aaron Norman Kenneth Offit Janet E Olson Håkan Olsson Nick Orr V Shane Pankratz Tjoung-Won Park-Simon Jose I A Perez Clara Pérez-Barrios Paolo Peterlongo Julian Peto Mila Pinchev Dijana Plaseska-Karanfilska Eric C Polley Ross Prentice Nadege Presneau Darya Prokofyeva Kristen Purrington Katri Pylkäs Brigitte Rack Paolo Radice Rohini Rau-Murthy Gad Rennert Hedy S Rennert Valerie Rhenius Mark Robson Atocha Romero Kathryn J Ruddy Matthias Ruebner Emmanouil Saloustros Dale P Sandler Elinor J Sawyer Daniel F Schmidt Rita K Schmutzler Andreas Schneeweiss Minouk J Schoemaker Fredrick Schumacher Peter Schürmann Lukas Schwentner Christopher Scott Rodney J Scott Caroline Seynaeve Mitul Shah Mark E Sherman Martha J Shrubsole Xiao-Ou Shu Susan Slager Ann Smeets Christof Sohn Penny Soucy Melissa C Southey John J Spinelli Christa Stegmaier Jennifer Stone Anthony J Swerdlow Rulla M Tamimi William J Tapper Jack A Taylor Mary Beth Terry Kathrin Thöne Rob A E M Tollenaar Ian Tomlinson Thérèse Truong Maria Tzardi Hans-Ulrich Ulmer Michael Untch Celine M Vachon Elke M van Veen Joseph Vijai Clarice R Weinberg Camilla Wendt Alice S Whittemore Hans Wildiers Walter Willett Robert Winqvist Alicja Wolk Xiaohong R Yang Drakoulis Yannoukakos Yan Zhang Wei Zheng Argyrios Ziogas Alison M Dunning Deborah J Thompson Georgia Chenevix-Trench Jenny Chang-Claude Marjanka K Schmidt Per Hall Roger L Milne Paul D P Pharoah Antonis C Antoniou Nilanjan Chatterjee Peter Kraft Montserrat García-Closas Jacques Simard Douglas F Easton

Am J Hum Genet 2018 Dec 5. Epub 2018 Dec 5.

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Read More

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December 2018

Daily oral cyanocobalamin supplementation in Beagles with hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome) maintains normal clinical and cellular cobalamin status.

J Vet Intern Med 2018 Dec 15. Epub 2018 Dec 15.

Department of Clinical Chemistry, University Children's Hospital Zurich, Zurich, Switzerland.

Background: Efficacy of PO cobalamin (Cbl) supplementation in dogs with hereditary Cbl malabsorption (Imerslund-Gräsbeck syndrome, IGS) is unknown.

Objectives: To evaluate PO Cbl supplementation in Beagles with IGS previously treated parenterally. We hypothesized that 1 mg cyano-Cbl daily PO would maintain clinical and metabolic remission. Read More

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December 2018
1 Read

Overcoming bioethical, legal, and hereditary barriers to mitochondrial replacement therapy in the USA.

J Assist Reprod Genet 2018 Dec 15. Epub 2018 Dec 15.

Exergen Corporation, Watertown, MA, USA.

The purpose of the paper is to explore novel means to overcome the controversial ban in the USA against mitochondrial replacement therapy, a form of IVF, with the added step of replacing a woman's diseased mutated mitochondria with a donor's healthy mitochondria to prevent debilitating and often fatal mitochondrial diseases. Long proven effective in non-human species, MRT recently performed in Mexico resulted in the birth of a healthy baby boy. We explore the ethics of the ban, the concerns over hereditability of mitochondrial disease and its mathematical basis, the overlooked role of Mitochondrial Eve, the financial burden of mitochondrial diseases for taxpayers, and a woman's reproductive rights. Read More

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December 2018

100 Years of phenogenetics: Valentin Haecker and his examination of the phenotype.

Mol Genet Genomics 2018 Dec 15. Epub 2018 Dec 15.

Research Group for Biology Education, Faculty of Biological Sciences, Institute of Zoology and Evolutionary Research, Friedrich-Schiller-University Jena, Am Steiger 3, Bienenhaus, 07743, Jena, Germany.

Following the 'rediscovery' of Mendel's work around 1900 the study of genetics grew rapidly and multiple new inheritance theories quickly emerged such as Hugo de Vries' "Mutation Theory" (1901) and the "Boveri-Sutton Chromosome Theory" (1902). Mendel's work also caught the attention of the German geneticist Valentin Haecker, yet he was generally dissatisfied the simplicity of Mendelian genetics as he believed that inheritance and the expression of various characteristics appeared to be much more complex than the proposed "on-off hypotheses". Haecker's primary objection was that Mendelian-based theories still failed to bridge the gap between hereditary units and phenotypic traits. Read More

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December 2018

A Family with Autosomal Dominant Distal Renal Tubular Acidosis Presents with Atypical Phenotype Caused by a Missence Mutation (R388C) of the Human Kidney Anion Exchanger.

Nephron 2018 Dec 14:1-6. Epub 2018 Dec 14.

Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang,

Hereditary forms of distal renal tubular acidosis (dRTA) are rare and mainly caused by mutations in ATP6V1B1, ATP6V0A4 and SLC4A1. About 20 mutations in SLC4A1 gene have been found that are related to either autosomal dominant (AD) or autosomal recessive dRTA. AD dRTA often manifest as constitutional and can easily be delayed in diagnosis and treatment. Read More

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December 2018

Screening and characterization of BRCA2 c.156_157insAlu in Brazil: Results from 1380 individuals from the South and Southeast.

Cancer Genet 2018 Dec 6;228-229:93-97. Epub 2018 Oct 6.

Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil; Barretos School of Health Science, Dr. Paulo Prata. Av. Loja Maçonica Renovadora, 68. Barretos 14785-002, São Paulo, Brazil. Electronic address:

Portuguese immigration to Brazil occurred in several waves and greatly contributed to the genetic composition of current Brazilian population. In this study, we evaluated the frequency of a Portuguese founder Alu insertion in BRCA2 exon 3 (c.156_157insAlu) among individuals fulfilling Hereditary Breast and Ovarian Cancer (HBOC) syndrome criteria in 1,380 unrelated families originated from three distinct Brazilian States. Read More

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December 2018

New insights into the performance of multigene panel testing: Two novel nonsense variants in BRIP1 and TP53 in a young woman with breast cancer.

Cancer Genet 2018 Dec 23;228-229:1-4. Epub 2018 Jun 23.

Genetic Diagnostic Laboratory, Department of Clinical Analyses, Clinical University Hospital Virgen Arrixaca, Ctra Murcia-Cartagena s/n. El Palmar, 30120 Murcia, Spain.

Li-Fraumeni syndrome is an autosomal-dominant disorder caused by germline mutations in the tumour suppressor gene TP53. Here we report the case of a family whose index case was a woman diagnosed with bilateral breast cancer at the age of 18 and who had a non-informative result after BRCA1 and BRCA2 testing. After extending the study through multigene panel testing, two clinically relevant variants in the TP53 and BRIP1 genes, respectively, were found. Read More

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December 2018

Hereditary cardiac amyloidosis associated with Pro24Ser transthyretin mutation: a case report.

J Med Case Rep 2018 Dec 16;12(1):370. Epub 2018 Dec 16.

Department of Clinical Research, Chiba Tokushukai Hospital, Chiba, Japan.

Background: Transthyretin amyloidosis is a systemic disorder caused by extracellular deposition of insoluble amyloid fibrils in peripheral and autonomic nerves, heart, kidney, gastrointestinal tract, and other organs. Hereditary transthyretin amyloidosis is an autosomal dominant disease. More than 120 mutations have been reported in the transthyretin gene with considerable phenotypic heterogeneity and geographic diversity. Read More

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December 2018
1 Read

Defective repair capacity of variant proteins of the DNA glycosylase NTHL1 for 5-hydroxyuracil, an oxidation product of cytosine.

Free Radic Biol Med 2018 Dec 12. Epub 2018 Dec 12.

Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

The NTHL1 gene encodes DNA glycosylase, which is involved in base excision repair, and biallelic mutations of this gene result in NTHL1-associated polyposis (NAP), a hereditary disease characterized by colorectal polyposis and multiple types of carcinomas. However, no proper functional characterization of variant NTHL1 proteins has been done so far. Herein, we report functional evaluation of variant NTHL1 proteins to aid in the accurate diagnosis of NAP. Read More

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December 2018

Hereditary breast cancer; Genetic penetrance and current status with BRCA.

J Cell Physiol 2018 Dec 14. Epub 2018 Dec 14.

School of Medicine, Menzies Health Institute Queensland, Gold Coast, QLD.

The most important cause of developing hereditary breast cancer is germline mutations occurring in breast cancer (BCs) susceptibility genes, for example, BRCA1, BRCA2, TP53, CHEK2, PTEN, ATM, and PPM1D. Many BC susceptibility genes can be grouped into two classes, high- and low-penetrance genes, each of which interact with multiple genes and environmental factors. However, the penetrance of genes can also be represented by a spectrum, which ranges between high and low. Read More

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December 2018
3 Reads

Alternative transcript imbalance underlying breast cancer susceptibility in a family carrying PALB2 c.3201+5G>T.

Breast Cancer Res Treat 2018 Dec 14. Epub 2018 Dec 14.

Oncogenetics Group, Vall d'Hebron Institute of Oncology, VHIO, 08035, Barcelona, Spain.

Purpose: Disruption of splicing motifs by genetic variants can affect the correct generation of mature mRNA molecules leading to aberrant transcripts. In some cases, variants may alter the physiological transcription profile composed of several transcripts, and an accurate in vitro evaluation is crucial to establish their pathogenicity. In this study, we have characterized a novel PALB2 variant c. Read More

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December 2018

Development of transgenic Caenorhabditis elegans expressing human transthyretin as a model for drug screening.

Sci Rep 2018 Dec 14;8(1):17884. Epub 2018 Dec 14.

Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Familial amyloid polyneuropathy is a hereditary systemic amyloidosis caused by a mutation in the transthyretin (TTR) gene. Amyloid deposits in tissues of patients contain not only full-length TTR but also C-terminal TTR fragments. However, in vivo models to evaluate the pathogenicity of TTR fragments have not yet been developed. Read More

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December 2018

Acute Pancreatitis Caused by Ampullary Duodenum Adenoma in a Patient with Adenomatous Polyposis Coli with Billroth II Reconstruction After Distal Gastrectomy.

Am J Case Rep 2018 Dec 15;19:1495-1498. Epub 2018 Dec 15.

Department of Gastroenterology, Kita-Harima Medical Center, Ichiba, Ono, Hyogo, Japan.

BACKGROUND Adenomatous polyposis coli is an autosomal dominant hereditary disorder. Duodenal adenocarcinoma and adenoma, which are extracolonic lesions, not only affect the prognosis of patients but also cause acute pancreatitis. CASE REPORT We present the case of a 73-year-old male. Read More

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December 2018

Common genetic variants contribute to incomplete penetrance: evidence from cancer-free BRCA1 mutation carriers.

Eur J Cancer 2018 Dec 11;107:68-78. Epub 2018 Dec 11.

Department of Genetics, Cell Biology and Anatomy, College of Medicine, USA; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, SAR, China. Electronic address:

Purpose: The presence of pathogenic germline mutation in BRCA1 gene is considered as the most penetrant genetic predisposition for breast cancer. However, a portion of BRCA1 mutation carriers never develops breast cancer throughout their lifetime. This phenomenon is called incomplete penetrance. Read More

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December 2018

Survival and outcome in MELAS not only depends on onset and disease duration.

J Neurol Sci 2018 Dec 6;397:9-10. Epub 2018 Dec 6.

University of Tunis El Manar and Genomics Platform, Pasteur Institute of Tunis, Tunisia.

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December 2018

Development of a Health-Related Quality of Life (QoL) instrument for Patients with Hereditary Angioedema (HAE) living in the United States.

J Allergy Clin Immunol Pract 2018 Dec 11. Epub 2018 Dec 11.

Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, CA.

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December 2018

Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis.

Cell 2018 Dec;175(7):1931-1945.e18

Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA; The J. David Gladstone Institutes, San Francisco, CA, USA. Electronic address:

Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Read More

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December 2018
2 Reads

Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.

J Mol Cell Cardiol 2018 Dec 11. Epub 2018 Dec 11.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, United States. Electronic address:

Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Read More

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December 2018
1 Read

Recurrence of hereditary hemorrhagic telangiectasia after liver transplantation: clinical implications and physiopathological insights.

Hepatology 2018 Dec 14. Epub 2018 Dec 14.

Gustave Roussy Cancer Campus, Département de Biologie et Pathologie Médicales, Service de Pathologie Moléculaire, Villejuif.

Liver transplantation (LT) has been proposed as a curative treatment in hereditary hemorrhagic telangiectasia (HHT) with severe hepatic involvement. We provide a long-term evaluation of graft status after LT for HHT, with a focus on the risk of recurrence. The present study included all patients prospectively followed-up after LT for HHT in the Lyon liver transplant unit from 1993 to 2010, with a survival of more than 1 year. Read More

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December 2018

Improvement of hereditary palmoplantar keratoderma with oral trametinib.

Pediatr Dermatol 2018 Dec 12. Epub 2018 Dec 12.

Dermatology Program, Boston Children's Hospital, Boston, Massachusetts.

We report a child with a past medical history notable for congenital deafness, palmoplantar keratoderma (PPK), and hypothalamic glioma who initiated a MEK inhibitor trametinib for cancer-directed therapy at 11 years of age and was incidentally noted to have marked improvement in his PPK. Trametinib withdrawal led to worsening in the patient's PPK. We speculate that the patient's PPK improved because of trametinib, given the temporal relationship between trametinib therapy and PPK severity, observed both after introduction and withdrawal of trametinib therapy. Read More

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December 2018

Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in females with Type 1 diabetes.

J Diabetes Investig 2018 Dec 11. Epub 2018 Dec 11.

Laboratório de Carboidratos e Radioimunoensaio LIM-18, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR. Av. Dr. Arnaldo, 455São Paulo, SP, BR.

Aims/introduction: Epigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications.

Material And Methods: We assessed the frequency of 5 single nucleotide polymorphisms (SNPs) in the gene encoding DNA methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414, and rs10854076) and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy (CAN) in 359 long-term Type 1 diabetes individuals. Read More

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December 2018
1 Read

Eosin-5'-maleimide binding test-Do we use appropriate reference values to detect hereditary spherocytosis in neonates?

Int J Lab Hematol 2018 Dec 10. Epub 2018 Dec 10.

Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland.

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December 2018

TP53 somatic mutations are associated with somatic mitogenome substitutions but not indels in colorectal cancer cells.

J Gene Med 2018 Dec 10:e3063. Epub 2018 Dec 10.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.

Background: p53 is a tumour suppressor protein that is involved in many cancer-related processes. Growing evidence suggests that p53 also plays an important role in mtDNA maintenance. Somatic mitogenome mutations are frequently observed in colorectal cancer cells. Read More

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December 2018

Different outcomes in sporadic versus familial medullary thyroid cancer.

Head Neck 2018 Dec 11. Epub 2018 Dec 11.

Endocrine Unit, Department of Clinical Therapeutics, School of Medicine, National Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece.

Background: Medullary thyroid carcinoma (MTC) has varying clinical course with familial cases (fMTC) diagnosed earlier than sporadic MTC (spMTC).

Methods: A total of 273 MTCs (familial: n = 110 [40.3%], males: 38. Read More

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December 2018
1 Read

Comorbidity among HHT patients and their controls in a 20 years follow-up period.

Orphanet J Rare Dis 2018 Dec 14;13(1):223. Epub 2018 Dec 14.

Odense Patient data Explorative Network (OPEN), Odense University Hospital/Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Background: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disorder with a wide variety of clinical manifestations due to the presence of multiple arteriovenous malformations in various tissues and organs.

Objective: To study the need for hospital admittance in a group of HHT patients and matched controls during a 20 years follow-up period commencing in 1995.

Methods: All HHT patients in the County of Funen, Denmark, were included. Read More

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December 2018

A Life-Saving Palsy: Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) Presenting As Hand Weakness during Cardiopulmonary Resuscitation (CPR) Training

Ir Med J 2018 Sep 10;111(8):808. Epub 2018 Sep 10.

Department of Clinical Neurophysiology, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland.

Aim To describe a case of acute and transient hand weakness that developed during cardiopulmonary resuscitation (CPR) training. Hereditary neuropathy with liability to pressure palsies (HNPP) should be considered in patients with recurrent, painless motor or sensory neuropathies at sites of peripheral nerve compression. Methods Nerve conduction studies confirmed neuropraxia of the distal ulnar nerve with a mild background demyelinating peripheral neuropathy. Read More

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September 2018

Early Hereditary Diffuse Gastric Cancer (eHDGC) is Characterized by Subtle Genomic Instability and Active DNA Damage Response.

Pathol Oncol Res 2018 Dec 13. Epub 2018 Dec 13.

Division of Biomedical Science and Biochemistry, Research School of Biology, ANU College of Medicine, Biology and Environment, Australian National University, P.O. Box: 2601, Canberra, Australia.

Diffuse gastric cancer (DGC) is one of the two primary types of stomach cancer. Carriers of germline mutations in the gene encoding E-cadherin are predisposed to DGC. The primary aim of the present study was to determine if genomic instability is an early event in DGC and how it may lead to disease progression. Read More

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December 2018
3 Reads
1.806 Impact Factor

Immunoprofiles of colorectal cancer from Lynch syndrome.

Oncoimmunology 2019 26;8(1):e1515612. Epub 2018 Sep 26.

The Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark.

Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors. Read More

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September 2018
4 Reads

Downregulation of Neuronal and Dendritic Connexin36-Made Electrical Synapses Without Glutamatergic Axon Terminals in Spinal Anterior Horn Cells From the Early Stage of Amyotrophic Lateral Sclerosis.

Front Neurosci 2018 28;12:894. Epub 2018 Nov 28.

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases. Read More

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November 2018
2 Reads

Somatic and germline genomics in paediatric acute lymphoblastic leukaemia.

Nat Rev Clin Oncol 2018 Dec 13. Epub 2018 Dec 13.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.

Advances in genomic research and risk-directed therapy have led to improvements in the long-term survival and quality of life outcomes of patients with childhood acute lymphoblastic leukaemia (ALL). The application of next-generation sequencing technologies, especially transcriptome sequencing, has resulted in the identification of novel molecular subtypes of ALL with prognostic and therapeutic implications, as well as cooperative mutations that account for much of the heterogeneity in clinical responses observed among patients with specific ALL subtypes. In addition, germline genetic variants have been shown to influence the risk of developing ALL and/or the responses of non-malignant and leukaemia cells to therapy; shared pathways for drug activation and metabolism are implicated in treatment-related toxicity and drug sensitivity or resistance, depending on whether the genetic changes are germline, somatic or both. Read More

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December 2018
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Structural Features of Heparan Sulfate from Multiple Osteochondromas and Chondrosarcomas.

Molecules 2018 Dec 11;23(12). Epub 2018 Dec 11.

Department of Medical Genetics and Rare Orthopaedic Diseases & CLIBI Laboratory-IRCCS, Istituto Ortopedico Rizzoli, V. di Barbiano 1/10, 40136 Bologna, Italy.

Multiple osteochondromas (MO) is a hereditary disorder associated with benign cartilaginous tumors, known to be characterized by absence or highly reduced amount of heparan sulfate (HS) in the extracellular matrix of growth plate cartilage, which alters proper signaling networks leading to improper bone growth. Although recent studies demonstrated accumulation of HS in the cytoplasm of MO chondrocytes, nothing is known on the structural alterations which prevent HS from undergoing its physiologic pathway. In this work, osteochondroma (OC), peripheral chondrosarcoma, and healthy cartilaginous human samples were processed following a procedure previously set up to structurally characterize and compare HS from pathologic and physiologic conditions, and to examine the phenotypic differences that arise in the presence of either exostosin 1 or 2 ( or ) mutations. Read More

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December 2018

PROS1 IVS10+5G>A mutation causes hereditary protein S deficiency in a Chinese patient with pulmonary embolism and venous thromboembolism.

Thromb Res 2018 Dec 6;174:1-4. Epub 2018 Dec 6.

Division of Vascular Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

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December 2018

Microsatellite instability in colorectal cancer: overview of its clinical significance and novel perspectives.

Clin Adv Hematol Oncol 2018 Nov;16(11):735-745

Levine Cancer Institute of the Carolinas HealthCare System, Charlotte, North Carolina.

Microsatellite instability (MSI) is a key biomarker in colorectal cancer (CRC), with crucial diagnostic, prognostic, and predictive implications. Testing for mismatch repair deficiency (MMR-D)/MSI is recommended during screening for Lynch syndrome, an autosomal-dominant hereditary disease that is characterized by germline mutations in the MMR genes and associated with an increased risk for several types of cancer. Additionally, MSI-high (MSI-H) status is associated with a better prognosis in early-stage CRC and a lack of benefit from adjuvant treatment with 5-fluorouracil in stage II disease. Read More

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November 2018

Next Generation Sequencing in Molecular Diagnosis of Lynch Syndrome - a Pilot Study Using New Stratification Criteria.

Acta Medica (Hradec Kralove) 2018 ;61(3):98-102

Department of Molecular Biology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia.

The development of the new technologies such as the next-generation sequencing (NGS) makes more accessible the diagnosis of genetically heterogeneous diseases such as Lynch syndrome (LS). LS is one of the most common hereditary form of colorectal cancer. This autosomal dominant inherited disorder is caused by deleterious germline mutations in one of the mismatch repair (MMR) genes - MLH1, MSH2, MSH6 or PMS2, or the deletion in the EPCAM gene. Read More

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January 2018
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Genetic analysis of a case of Helicobacter pylori-uninfected intramucosal gastric cancer in a family with hereditary diffuse gastric cancer.

Gastric Cancer 2018 Dec 12. Epub 2018 Dec 12.

Kansai Electric Power Hospital, Osaka, Japan.

Germline mutations in CDH1, encoding E-cadherin, are known to be the causative mechanism of hereditary diffuse gastric cancer (HDGC). We encountered two cases of gastric cancer in a Japanese family with HDGC. A 28-year-old man (Case 1) died of advanced gastric cancer. Read More

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December 2018

Structure of native lens connexin 46/50 intercellular channels by cryo-EM.

Nature 2018 Dec 12. Epub 2018 Dec 12.

Department of Chemistry, Portland State University, Portland, OR, USA.

Gap junctions establish direct pathways for cell-to-cell communication through the assembly of twelve connexin subunits that form intercellular channels connecting neighbouring cells. Co-assembly of different connexin isoforms produces channels with unique properties and enables communication across cell types. Here we used single-particle cryo-electron microscopy to investigate the structural basis of connexin co-assembly in native lens gap junction channels composed of connexin 46 and connexin 50 (Cx46/50). Read More

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December 2018

Low Prevalence of the Four Common Colombian Founder Mutations in and in Early-Onset and Familial Afro-Colombian Patients with Breast Cancer.

Oncologist 2018 Dec 12. Epub 2018 Dec 12.

Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany.

Background: Inherited mutations in the breast cancer susceptibility genes and () confer high risks of breast and ovarian cancer. In Colombian Hispanic families, four common founder mutations have previously been identified. Because nothing is known about the contribution of germline mutations to early-onset and hereditary breast and/or ovarian cancer in Afro-Colombians, we conducted the first study on 60 patients with early-onset and familial breast cancer in this population. Read More

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December 2018

Is chronic use of hydroxyurea safe for patients with sickle cell anemia? An account of genotoxicity and mutagenicity.

Environ Mol Mutagen 2018 Dec 7. Epub 2018 Dec 7.

Faculty of Pharmacy, Federal University of Ceará, Fortaleza, Brazil.

Sickle cell anemia (SCA) is a hereditary hematological disease that is characterized by a point mutation in the beta globin S gene and has no specific treatment; hydroxyurea (HU) is the only therapeutic agent used in clinical practice. In the present study, we evaluated the deoxyribonucleic acid (DNA) damage index (DI) and chromosomal damage in leukocytes of adult patients with SCA with and without HU. The DI was assessed by the comet assay and chromosomal damage by the leukocyte micronucleus test of adult patients treated with HU (SCA-HU) and without the use of HU (SCA-NoHU). Read More

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December 2018

Next Generation Sequencing in Clinical Oncology: Applications, Challenges and Promises: A Review Article.

Iran J Public Health 2018 Oct;47(10):1453-1457

Zoonosis Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: The aim of this mini-review is to highlight the potential applications of next-generation sequencing technology to the field of clinical oncology with respect to genetic diagnosis, cancer classification, predictive biomarkers and personalized medicine.

Methods: Scientific databases were searched to collect relative data.

Results: Effective systematic analysis of whole-genome sequence and whole-exome sequence of tumors, targeted genome profiling, transcriptome sequencing and tumor-normal comparisons can be performed using NGS in order to diagnosis of several types of cancer. Read More

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October 2018