Incorrect Dosage of IQSEC2, a Known Intellectual Disability and Epilepsy Gene, Disrupts Dendritic Spine Morphogenesis
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Multiple Interactions Between an Arf/GEF Complex and Charged Lipids Determine Activation Kinetics on the Membrane
Multiple interactions between an Arf/GEF complex and charged lipids determine activation kinetics on the membrane Deepti Karandura,b,1, Agata Nawrotekc,d,1, John Kuriyana,b,2, and Jacqueline Cherfilsc,d,2 aDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720; bHoward Hughes Medical Institute, University of California, Berkeley, CA 94720; cLaboratoire de Biologie et Pharmacologie Appliquée, CNRS, Cachan 94235, France; and dEcole Normale Supérieure Paris-Saclay, Cachan 94235, France Edited by Satyajit Mayor, National Centre for Biological Sciences, Bangalore, India, and approved August 28, 2017 (received for review May 15, 2017) Lipidated small GTPases and their regulators need to bind to which is surrounded by an assortment of regulatory domains (9). membranes to propagate actions in the cell, but an integrated Sec7-assisted nucleotide exchangeoccursinastep-by-step manner, understanding of how the lipid bilayer exerts its effect has whereby the Sec7 domain binds to the switch 1 and switch 2 regions remained elusive. Here we focused on ADP ribosylation factor of Arf to remodel the interswitch and inserts an invariant gluta- (Arf) GTPases, which orchestrate a variety of regulatory functions mate into the nucleotide-binding site to displace GDP (6, 7, 10). in lipid and membrane trafficking, and their activation by the In metazoans, Arf GTPases are activated at the plasma mem- guanine-nucleotide exchange factor (GEF) Brag2, which controls brane and on endosomes by members of three ArfGEF subfamilies: integrin endocytosis and cell adhesion and is impaired in cancer cytohesins, EFA6, and Brag/IQSEC. These ArfGEFs share a com- and developmental diseases. Biochemical and structural data are mon organization in which the Sec7 domain is immediately followed available that showed the exceptional efficiency of Arf activation by a pleckstrin homology (PH) domain that binds phosphoinositide by Brag2 on membranes. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Gen- Symbol Genname Erkrankung(En) OMIM Gengröße
Gen‐ Gengröße Genname Erkrankung(en) OMIM symbol (kb) Arterial calcification, generalized, of infancy, 2 614473 ABCC6 ATP‐BINDING CASSETTE, SUBFAMILY C, MEMBER 6 Pseudoxanthoma elasticum 264800 4,5 Pseudoxanthoma elasticum, forme fruste 177850 ACSL4 ACYL‐CoA SYNTHETASE LONG CHAIN FAMILY, MEMBER 4 Mental retardation, X‐linked 63 300387 2,1 AFF2 AF4/FMR2 FAMILY, MEMBER 2 (FMR2) Mental retardation, X‐linked, FRAXE type 309548 3,9 APOPTOSIS‐INDUCING FACTOR, MITOCHONDRION‐ASSOCIATED, 1 Combined oxidative phosphorylation deficiency 6 300816 AIFM1 1,8 (PDCD8) Cowchock syndrome 310490 Proteus syndrome, somatic 176920 AKT1 V‐AKT MURINE THYMOMA VIRAL ONCOGENE HOMOLOG 1 1,4 Cowden syndrome 6 615109 Megalencephaly‐polymicrogyria‐polydactyly‐hydrocephalus AKT3 V‐AKT MURINE THYMOMA VIRAL ONCOGENE HOMOLOG 3 (PKBG) 615937 1,4 syndrome 2 AP1S2 ADAPTOR‐RELATED PROTEIN COMPLEX 1, SIGMA‐2 SUBUNIT Mental retardation, X‐linked syndromic 5 304340 0,5 ARHGEF6 RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 6 (PIXA) Mental retardation, X‐linked 46 300436 2,3 ARHGEF9 RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 9 (PEM2) Epileptic encephalopathy, early infantile, 8 300607 1,6 ARID1A AT‐RICH INTERACTION DOMAIN‐CONTAINING PROTEIN 1A (SMARCF1) Coffin‐Siris syndrome 2 614607 6,9 ARID1B AT‐RICH INTERACTION DOMAIN‐CONTAINING PROTEIN 1B Coffin‐Siris syndrome 1 135900 6,7 Epileptic encephalopathy, early infantile, 1 308350 Hydranencephaly with abnormal genitalia 300215 Lissencephaly, X‐linked 2 300215 ARX ARISTALESS‐RELATED HOMEOBOX, X‐LINKED 1,7 Mental retardation, X‐linked 29 and others -
1 Novel Expression Signatures Identified by Transcriptional Analysis
ARD Online First, published on October 7, 2009 as 10.1136/ard.2009.108043 Ann Rheum Dis: first published as 10.1136/ard.2009.108043 on 7 October 2009. Downloaded from Novel expression signatures identified by transcriptional analysis of separated leukocyte subsets in SLE and vasculitis 1Paul A Lyons, 1Eoin F McKinney, 1Tim F Rayner, 1Alexander Hatton, 1Hayley B Woffendin, 1Maria Koukoulaki, 2Thomas C Freeman, 1David RW Jayne, 1Afzal N Chaudhry, and 1Kenneth GC Smith. 1Cambridge Institute for Medical Research and Department of Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK 2Roslin Institute, University of Edinburgh, Roslin, Midlothian, EH25 9PS, UK Correspondence should be addressed to Dr Paul Lyons or Prof Kenneth Smith, Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0XY, UK. Telephone: +44 1223 762642, Fax: +44 1223 762640, E-mail: [email protected] or [email protected] Key words: Gene expression, autoimmune disease, SLE, vasculitis Word count: 2,906 The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Annals of the Rheumatic Diseases and any other BMJPGL products to exploit all subsidiary rights, as set out in their licence (http://ard.bmj.com/ifora/licence.pdf). http://ard.bmj.com/ on September 29, 2021 by guest. Protected copyright. 1 Copyright Article author (or their employer) 2009. -
EGL Test Description
2460 Mountain Industrial Boulevard | Tucker, Georgia 30084 Phone: 470-378-2200 or 855-831-7447 | Fax: 470-378-2250 eglgenetics.com Epilepsy and Seizure Disorders Panel: Sequencing and CNV Analysis Test Code: MEPI1 Turnaround time: 6 weeks CPT Codes: 81404 x1, 81406 x1, 81405 x1, 81175 x1, 81302 x1, 81403 x1, 81407 x1, 81409 x1, 81479 x1 Condition Description Epilepsy is defined as a disorder in which an individual has recurrent, unprovoked seizures. It has a prevalence of about 5-10 per 1000 people. While the causes of epilepsy are diverse, a significant proportion are considered to be genetic in origin. Epilepsy can occur as part of a clinical spectrum that is associated with a particular genetic syndrome, such as Mowat Wilson syndrome, Dravet syndrome, and “chromosomal” epilepsies. Common “chromosomal” epilepsies include 1p36 deletion syndrome, Wolf-Hirschhorn syndrome, Angelman syndrome, Miller-Dieker syndrome, 15q inversion- duplication, Down syndrome and ring chromosome 14 and 20. In addition, epilepsy can occur as an isolated finding, 40% of which are believed to be due to genetic causes. Approximately 2% of the genetic causes of isolated epilepsy are due to monogenetic causes while the rest are thought to be due to multifactorial genetic and environmental causes. Of the monogenetic genes identified, the majority code for ion channel subunits and neurotransmitter receptors. The Epilepsy and Seizure Disorders Panel is comprised of a next generation sequencing (NGS) for syndromic and non-syndromic causes of seizures. It is recommended that individuals with seizures have a chromosomal microarray as a first tier test. Please click here for information on our EmArray Cyto and CytoScan SNP Array. -
Perkinelmer Genomics to Request the Saliva Swab Collection Kit for Patients That Cannot Provide a Blood Sample As Whole Blood Is the Preferred Sample
Autism and Intellectual Disability TRIO Panel Test Code TR002 Test Summary This test analyzes 2429 genes that have been associated with Autism and Intellectual Disability and/or disorders associated with Autism and Intellectual Disability with the analysis being performed as a TRIO Turn-Around-Time (TAT)* 3 - 5 weeks Acceptable Sample Types Whole Blood (EDTA) (Preferred sample type) DNA, Isolated Dried Blood Spots Saliva Acceptable Billing Types Self (patient) Payment Institutional Billing Commercial Insurance Indications for Testing Comprehensive test for patients with intellectual disability or global developmental delays (Moeschler et al 2014 PMID: 25157020). Comprehensive test for individuals with multiple congenital anomalies (Miller et al. 2010 PMID 20466091). Patients with autism/autism spectrum disorders (ASDs). Suspected autosomal recessive condition due to close familial relations Previously negative karyotyping and/or chromosomal microarray results. Test Description This panel analyzes 2429 genes that have been associated with Autism and ID and/or disorders associated with Autism and ID. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis is designed to detect the majority of deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines. Condition Description Autism Spectrum Disorder (ASD) refers to a group of developmental disabilities that are typically associated with challenges of varying severity in the areas of social interaction, communication, and repetitive/restricted behaviors. -
SF3B1-Mutated Chronic Lymphocytic Leukemia Shows Evidence Of
SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation by Federico Pozzo, Tamara Bittolo, Erika Tissino, Filippo Vit, Elena Vendramini, Luca Laurenti, Giovanni D'Arena, Jacopo Olivieri, Gabriele Pozzato, Francesco Zaja, Annalisa Chiarenza, Francesco Di Raimondo, Antonella Zucchetto, Riccardo Bomben, Francesca Maria Rossi, Giovanni Del Poeta, Michele Dal Bo, and Valter Gattei Haematologica 2020 [Epub ahead of print] Citation: Federico Pozzo, Tamara Bittolo, Erika Tissino, Filippo Vit, Elena Vendramini, Luca Laurenti, Giovanni D'Arena, Jacopo Olivieri, Gabriele Pozzato, Francesco Zaja, Annalisa Chiarenza, Francesco Di Raimondo, Antonella Zucchetto, Riccardo Bomben, Francesca Maria Rossi, Giovanni Del Poeta, Michele Dal Bo, and Valter Gattei SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation. Haematologica. 2020; 105:xxx doi:10.3324/haematol.2020.261891 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will -
Novel and De Novo Mutations in Pediatric Refractory Epilepsy Jing Liu1,2, Lili Tong1,2, Shuangshuang Song3, Yue Niu1,2, Jun Li1,2, Xiu Wu1,2, Jie Zhang4, Clement C
Liu et al. Molecular Brain (2018) 11:48 https://doi.org/10.1186/s13041-018-0392-5 RESEARCH Open Access Novel and de novo mutations in pediatric refractory epilepsy Jing Liu1,2, Lili Tong1,2, Shuangshuang Song3, Yue Niu1,2, Jun Li1,2, Xiu Wu1,2, Jie Zhang4, Clement C. Zai5, Fang Luo4, Jian Wu4, Haiyin Li5, Albert H. C. Wong5, Ruopeng Sun1,2, Fang Liu2,5 and Baomin Li1,2* Abstract Pediatric refractory epilepsy is a broad phenotypic spectrum with great genetic heterogeneity. Next-generation sequencing (NGS) combined with Sanger sequencing could help to understand the genetic diversity and underlying disease mechanisms in pediatric epilepsy. Here, we report sequencing results from a cohort of 172 refractory epilepsy patients aged 0–14 years. The pathogenicity of identified variants was evaluated in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria. We identified 43 pathogenic or likely pathogenic variants in 40 patients (23.3%). Among these variants, 74.4% mutations (32/43) were de novo and 60.5% mutations (26/43) were novel. Patients with onset age of seizures ≤12 months had higher yields of deleterious variants compared to those with onset age of seizures > 12 months (P = 0.006). Variants in ion channel genes accounted for the greatest functional gene category (55.8%), with SCN1A coming first (16/43). 81.25% (13/16) of SCN1A mutations were de novo and 68.8% (11/16) were novel in Dravet syndrome. Pathogenic or likely pathogenic variants were found in the KCNQ2, STXBP1, SCN2A genes in Ohtahara syndrome. Novel deleterious variants were also found in West syndrome, Doose syndrome and glucose transporter type 1 deficiency syndrome patients. -
Original Article Integrative Analysis of Somatic Mutations and Differential Expression Profiles in Glioblastoma Based on Aging Acceleration
Int J Clin Exp Pathol 2021;14(5):582-595 www.ijcep.com /ISSN:1936-2625/IJCEP0121428 Original Article Integrative analysis of somatic mutations and differential expression profiles in glioblastoma based on aging acceleration Huize Wang1,2, Shiyan Li3, Hongxin Liu3, Shiyu Bian4, Wanjiang Huang5, Chengzhong Xing2, Yin Wang2,3 1Department of Nursing, First Affiliated Hospital of China Medical University, 155# North Nanjing Street, Shenyang 110001, Liaoning, China; 2Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, 155# North Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China; 3Department of Biomedical Engineering, School of Fundamental Sciences, China Medical University, Shenyang 110122, Liaoning Province, China; 4China Medical University - The Queen’s University of Belfast Joint College, China Medical University, Shenyang 110122, Liaoning Province, China; 5No. 10 Middle School, Xiangyang 441021, Hubei Province, China Received August 31, 2020; Accepted February 7, 2021; Epub May 15, 2021; Published May 30, 2021 Abstract: Background: Glioblastoma (GBM) is an aggressive brain tumor and the mechanisms of progression are very complex. Accelerated aging is a driving factor of GBM. However, there has not been thorough research about the mechanisms of GBM progression based on aging acceleration. Methods: The aging predictor was modeled based on normal brain samples. Then an aging acceleration background network was constructed to explore GBM mechanisms. Results: The accelerated aging-related mechanisms provided an innovative way to study GBM, where- in integrative analysis of somatic mutations and differential expression revealed key pathologic characteristics. Moreover, the influence of the immune system, the nervous system and other critical factors on GBM were identi- fied. -
Epilepsy Next-Generation Sequencing Guide
Phenotype-based Neurology Next-Generation Sequencing with Epilepsy Copy Number Variant Analysis Generalized, Absence, Focal, Febrile, and Myoclonic Epilepsies Epileptic Encephalopathy Developmental Brain Malformations Intellectual Disability Neuronal Ceroid Lipofuscinosis Epilepsy with Migraine Syndromic Disorders Infantile Spasms Now with 234 genes Getting a clearer picture of the causes of epilepsy Harnessing the power of NGS for earlier diagnosis Athena Diagnostics offers a comprehensive approach to diagnosing the causes of epilepsy, which may be helpful when considering different treatment options and avoiding contraindicated drugs. Our phenotypebased approach is supported by clinical diagnostic exome sequencing to provide molecular diagnosis for a significant proportion of patients with epilepsy.11 The benefits include: • An accurate diagnosis sooner at typically less cost Phenotype- When your patient presents with epilepsy based NGS than traditional methods testing with CNV analysis symptoms, the specific cause is not always • Reduced turnaround time (TAT) clear. Using next-generation sequencing • More informed future Athena Diagnostics (NGS) to uncover a genetic cause of planning for the patient NextGen and their family Fast, testing In-depth disease may lead to answers that can cost-efficient results NGS technology interpretation aid in identifying the most appropriate treatment and care for your patient. ® Athena Diagnostics provides NGS A comprehensive panel delivering actionable insights evaluations for epilepsy arranged by clinical Athena Diagnostics Epilepsy Advanced Sequencing and CNV phenotype, testing the most comprehensive Evaluations feature: collection of clinically-relevant genes • Nextgeneration sequencing and CNV testing for 234 genes known to be associated with epilepsy, • Phenotypeguided evaluations, making test selection easier and which streamlines the diagnostic process may help avoid costly, unnecessary testing and may save time and money. -
Perkinelmer Genomics to Request the Saliva Swab Collection Kit for Patients That Cannot Provide a Blood Sample As Whole Blood Is the Preferred Sample
STAT Focused Autism and Intellectual Disability Panel Test Code D5130F Test Summary This test analyzes 264 genes that have been associated with Autism and Intellectual Disability. STAT means results are available in 7 - 10 days. Turn-Around-Time (TAT)* 7 - 10 days Acceptable Sample Types Whole Blood (EDTA) (Preferred sample type) DNA, Isolated Dried Blood Spots Saliva Acceptable Billing Types Self (patient) Payment Institutional Billing Indications for Testing This panel may be appropriate for individuals with a clinical suspicion of Lissencephaly and/or for indiviudals with a family history of Lissencephaly. Test Description This panel analyzes 264 genes that have been associated with Focused Autism and Intellectual Disability and/or disorders associated with Focused Autism and Intellectual Disability. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis is designed to detect the majority of deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines. Condition Description Autism Spectrum Disorder (ASD) refers to a group of developmental disabilities that are typically associated with challenges of varying severity in the areas of social interaction, communication, -
Autocrine IFN Signaling Inducing Profibrotic Fibroblast Responses By
Downloaded from http://www.jimmunol.org/ by guest on September 23, 2021 Inducing is online at: average * The Journal of Immunology , 11 of which you can access for free at: 2013; 191:2956-2966; Prepublished online 16 from submission to initial decision 4 weeks from acceptance to publication August 2013; doi: 10.4049/jimmunol.1300376 http://www.jimmunol.org/content/191/6/2956 A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Autocrine IFN Signaling Feng Fang, Kohtaro Ooka, Xiaoyong Sun, Ruchi Shah, Swati Bhattacharyya, Jun Wei and John Varga J Immunol cites 49 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130037 6.DC1 This article http://www.jimmunol.org/content/191/6/2956.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 23, 2021. The Journal of Immunology A Synthetic TLR3 Ligand Mitigates Profibrotic Fibroblast Responses by Inducing Autocrine IFN Signaling Feng Fang,* Kohtaro Ooka,* Xiaoyong Sun,† Ruchi Shah,* Swati Bhattacharyya,* Jun Wei,* and John Varga* Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated ligands leads to production of type I IFN.