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Your search keyword '"Institute for Genomic Medicine [New York, NY, USA]"' showing total 4 results
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4 results on '"Institute for Genomic Medicine [New York, NY, USA]"'

1. Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains ofKCNH5

Author

Hannah C. Happ, Lynette G. Sadleir, Matthew Zemel, Guillem de Valles-Ibáñez, Michael S. Hildebrand, Allyn McConkie-Rosell, Marie McDonald, Halie May, Tristan Sands, Vimla Aggarwal, Christopher Elder, Timothy Feyma, Allan Bayat, Rikke S. Møller, Christina D. Fenger, Jens Erik Klint Nielsen, Anita N. Datta, Kathleen M. Gorman, Mary D. King, Natalia D. Linhares, Barbara K. Burton, Andrea Paras, Sian Ellard, Julia Rankin, Anju Shukla, Purvi Majethia, Rory J. Olson, Karthik Muthusamy, Lisa A. Schimmenti, Keith Starnes, Lucie Sedláčková, Katalin Štěrbová, Markéta Vlčková, Petra Laššuthová, Alena Jahodová, Brenda E. Porter, Nathalie Couque, Estelle Colin, Clément Prouteau, Corinne Collet, Thomas Smol, Roseline Caumes, Fleur Vansenne, Francesca Bisulli, Laura Licchetta, Richard Person, Erin Torti, Kirsty McWalter, Richard Webster, Elizabeth E. Gerard, Gaetan Lesca, Pierre Szepetowski, Ingrid E. Scheffer, Heather C. Mefford, Gemma L. Carvill, University of Otago [Dunedin, Nouvelle-Zélande], University of Washington [Seattle], Epilepsy Research Centre, University of Melbourne, Duke University Medical Center, Institute for Genomic Medicine [New York, NY, USA], Columbia University [New York], Columbia University Irving Medical Center (CUIMC), University of Southern Denmark (SDU), Zealand University Hospital [Roskilde, Denmark], University of British Columbia [Vancouver], University College Dublin [Dublin] (UCD), Kasturba Medical College, Manipal, Center for Individualized Medicine, Stanford University School of Medicine [CA, USA], Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut de Génétique Médicale [CHRU Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Bologna/Università di Bologna, GeneDx [Gaithersburg, MD, USA], Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurology (clinical), Research Article
Abstract

Background and ObjectivesKCNH5encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novoKCNH5variants.MethodsWe screened 893 individuals with developmental and epileptic encephalopathies forKCNH5variants using targeted or exome sequencing. Additional individuals withKCNH5variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details.ResultsWe report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.DiscussionWe describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establishKCNH5as implicated in a spectrum of neurodevelopmental disorders and epilepsy.

Published
2022
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2. Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1

Author

Xiaojiang Gao, Stephen A. Migueles, Steven G. Deeks, Bruce D. Walker, Florencia P Segal, Emma Gostick, Zabrina L. Brumme, Mary Carrington, James J. Goedert, Nelson L. Michael, Jonathan M. Carlson, Ying Qi, Patrick R. Shea, David Price, Steven M. Wolinsky, Vivek Naranbhai, Julian P. Vivian, Nicolas Vince, Rasmi Thomas, Sian Llewellyn-Lacey, Maureen P. Martin, Jacques Fellay, Bernard A. P. Lafont, Veron Ramsuran, Jamie Rossjohn, David W. Haas, Shu Cheng Wong, Andrew G. Brooks, Philippa M. Saunders, Mark Connors, Jacqueline M.L. Widjaja, Phillip Pymm, Cancer and Inflammation Program [Frederick, MD, USA] (Leidos Biomedical Research Inc.), Frederick National Laboratory for Cancer Research (FNLCR)-NCI-Frederick, Ragon Institute of MGH, MIT and Harvard, Centre for the AIDS Programme of Research [Durban, South Africa] (CAPRISA), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Institute for Genomic Medicine [New York, NY, USA], Columbia University [New York], KwaZulu-Natal Research Innovation and Sequencing Platform [Durban, South Africa] (KRISP), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-School of Laboratory Medicine and Medical Sciences [Durban, South Africa], Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Translational ImmunoGenetic in AutoImmunity and Transplantation (Team 5 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), US Military HIV Research Program [Silver Spring, MD, USA], Walter Reed Army Institute of Research, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), Faculty of Health Sciences [Burnaby, BC, Canada], Simon Fraser University (SFU.ca), British Columbia Centre for Excellence in HIV/AIDS [Vancouver, BC, Canada], Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Division of Infectious Diseases [Chicago, IL, USA], Northwestern University Feinberg School of Medicine, Infections and Immunoepidemiology Branch [Bethesda, MD, USA], National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), San Francisco General Hospital Medical Center [San Francisco, CA, USA], Vanderbilt University School of Medicine [Nashville], Laboratory of Immunoregulation [Bethesda, MD, USA], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], Non-Human Primate Immunogenetics and Cellular Immunology Unit [Bethesda, MD, USA], National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Deseases (NIAID), Human Immunology Section [Bethesda, MD, USA] (Vaccine Research Center), Viral Immunology Section [Bethesda, MD, USA] (Office of the Scientific Director), Infection and Immunity Program [Victoria, Australia] (Department of Biochemistry and Molecular Biology), Monash University [Clayton]-Biomedicine Discovery Institute [Victoria, Australia]-Australian Research Council Centre of Excellence in Advanced Molecular Imaging [Victoria, Australia], Department of Microbiology and Immunology [Victoria, Australia], University of Melbourne-Peter Doherty Institute for Infection and Immunity [Victoria, Australia], This work was supported by federal funds from the NCI, NIH, under contract HHSN261200800001E., Le Bihan, Sylvie, University of KwaZulu-Natal (UKZN), University of KwaZulu-Natal (UKZN)-School of Laboratory Medicine and Medical Sciences [Durban, South Africa], Institute of Medical Genetics [Cardiff]-Cardiff University, and Monash University [Clayton]-Australian Research Council Centre of Excellence in Advanced Molecular Imaging [Victoria, Australia]-Biomedicine Discovery Institute [Victoria, Australia]

Subjects
0301 basic medicine, Adult, Male, T cell, Killer-cell immunoglobulin-like receptor, Immunology, HIV Infections, NK cells, Medical and Health Sciences, AIDS/HIV, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, KIR3DL1, Clinical Research, MHC class I, Receptors, medicine, HLA-B Antigens, 2.1 Biological and endogenous factors, Humans, Aetiology, Receptor, MHC class 1, Innate immunity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Genetic Variation, Receptors, KIR3DL1, General Medicine, Middle Aged, Molecular biology, Allotype, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Good Health and Well Being, biology.protein, HIV-1, HIV/AIDS, Female, Infection, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Research Article
Abstract

International audience; HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57+ individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1 allotypes differing only at these 3 positions showed significant differences in binding B*57:01 tetramers, whereas the protective allotype showed lower binding. Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease.

Published
2017

3. Cognitive deficits in the Snord116 deletion mouse model for Prader-Willi syndrome.

Author

Adhikari A, Copping NA, Onaga B, Pride MC, Coulson RL, Yang M, Yasui DH, LaSalle JM, and Silverman JL

Subjects
Animals, Cognitive Dysfunction etiology, Disease Models, Animal, Humans, Mice, Prader-Willi Syndrome complications, Cognitive Dysfunction genetics, Gene Deletion, Prader-Willi Syndrome genetics, RNA, Small Nucleolar genetics
Abstract

Prader-Willi syndrome (PWS) is an imprinted neurodevelopmental disease caused by a loss of paternal genes on chromosome 15q11-q13. It is characterized by cognitive impairments, developmental delay, sleep abnormalities, and hyperphagia often leading to obesity. Clinical research has shown that a lack of expression of SNORD116, a paternally expressed imprinted gene cluster that encodes multiple copies of a small nucleolar RNA (snoRNA) in both humans and mice, is most likely responsible for many PWS symptoms seen in humans. The majority of previous research using PWS preclinical models focused on characterization of the hyperphagic and metabolic phenotypes. However, a crucial understudied clinical phenotype is cognitive impairments and thus we investigated the learning and memory abilities using a model of PWS, with a heterozygous deletion in Snord116. We utilized the novel object recognition task, which doesn't require external motivation, or exhaustive swim training. Automated findings were further confirmed with manual scoring by a highly trained blinded investigator. We discovered deficits in Snord116+/- mutant mice in the novel object recognition, location memory and tone cue fear conditioning assays when compared to age-, sex- matched, littermate control Snord116+/+ mice. Further, we confirmed that despite physical neo-natal developmental delays, Snord116+/- mice had normal exploratory and motor abilities. These results show that the Snord116+/- deletion murine model is a valuable preclinical model for investigating learning and memory impairments in individuals with PWS without common confounding phenotypes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2019
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4. TRPC Channels and Mental Disorders.

Author

Griesi-Oliveira K, Suzuki AM, and Muotri AR

Subjects
Animals, Disease Models, Animal, Humans, Mental Disorders genetics, Mice, Mice, Knockout, TRPC Cation Channels genetics, Brain metabolism, Calcium metabolism, Mental Disorders metabolism, TRPC Cation Channels metabolism
Abstract

Transient receptor potential canonical (TRPC) channels mediate the influx of different types of cations through the cell membrane and are involved in many functions of the organism. Evidences of involvement of TRPC channels in neuronal development suggest that this family of proteins might play a role in certain neurological disorders. As reported, knockout mice for different TRPC channels show alterations in neuronal morphological and functional parameters, with behavioral abnormalities, such as in exploratory and social behaviors. Although mutations in TRPC channels could be related to mental/neurological disorders, there are only a few cases reported in literature, indicating that this correlation should be further explored. Nonetheless, other functional evidences support the implication of these channels in neurological diseases. In this chapter, we summarize the main findings relating TRPC channels to neurological disorders, such as autism spectrum disorders, bipolar disorder, and intellectual disability among others.

Published
2017
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