Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25258
Title: NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns.
Austin Authors: Stamberger, Hannah;Hammer, Trine B;Gardella, Elena;Vlaskamp, Danique R M;Bertelsen, Birgitte;Mandelstam, Simone;de Lange, Iris;Zhang, Jing;Myers, Candace T;Fenger, Christina;Afawi, Zaid;Almanza Fuerte, Edith P;Andrade, Danielle M;Balcik, Yunus;Ben Zeev, Bruria;Bennett, Mark F ;Berkovic, Samuel F ;Isidor, Bertrand;Bouman, Arjan;Brilstra, Eva;Busk, Øyvind L;Cairns, Anita;Caumes, Roseline;Chatron, Nicolas;Dale, Russell C;de Geus, Christa;Edery, Patrick;Gill, Deepak;Granild-Jensen, Jacob Bie;Gunderson, Lauren;Gunning, Boudewijn;Heimer, Gali;Helle, Johan R;Hildebrand, Michael S ;Hollingsworth, Georgie;Kharytonov, Volodymyr;Klee, Eric W;Koeleman, Bobby P C;Koolen, David A;Korff, Christian;Küry, Sébastien;Lesca, Gaetan;Lev, Dorit;Leventer, Richard J;Mackay, Mark T;Macke, Erica L;McEntagart, Meriel;Mohammad, Shekeeb S;Monin, Pauline;Montomoli, Martino;Morava, Eva;Moutton, Sebastien;Muir, Alison M;Parrini, Elena;Procopis, Peter;Ranza, Emmanuelle;Reed, Laura;Reif, Philipp S;Rosenow, Felix;Rossi, Massimiliano;Sadleir, Lynette G;Sadoway, Tara;Schelhaas, Helenius J;Schneider, Amy L ;Shah, Krati;Shalev, Ruth;Sisodiya, Sanjay M;Smol, Thomas;Stumpel, Connie T R M;Stuurman, Kyra;Symonds, Joseph D;Mau-Them, Frederic Tran;Verbeek, Nienke;Verhoeven, Judith S;Wallace, Geoffrey;Yosovich, Keren;Zarate, Yuri A;Zerem, Ayelet;Zuberi, Sameer M;Guerrini, Renzo;Mefford, Heather C;Patel, Chirag;Zhang, Yue-Hua;Møller, Rikke S;Scheffer, Ingrid E 
Affiliation: INSERM UMR1231 GAD, Dijon, France
Department of Neurosciences, Queensland Children's Hospital, Brisbane, QLD, Australia
Epilepsy Research Centre, Department of Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
Department of Medical Biology University of Melbourne, Melbourne, VIC, Australia
Royal Children's Hospital, Melbourne, VIC, Australia
Murdoch Children's Research Institute, Melbourne, VIC, Australia
Department of Pediatrics, University of Melbourne, Melbourne, VIC, Australia
Department of Radiology, University of Melbourne, Melbourne, VIC, Australia
Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia
Department of Epilepsy Genetics, Danish Epilepsy Centre Filadelfia, Dianalund, Denmark
Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark
Applied and Translational Neurogenomics group, Center for Molecular Neurology, VIB, and Department of Neurology, University Hospital of Antwerp, University of Antwerp, Antwerpen, Belgium
Lyon University Hospitals, Departments of Genetics, Lyon, France
INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Bron, France
Edmond and Lily Safra Children's Hospital, Pediatric Neurology Unit, Tel-Hashomer, Israel
Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel
University of Groningen, University Medical Center Groningen, Department of Neurology, Groningen, the Netherlands
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
Clinical Genetic Department, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
CPDPN, Pôle mère enfant, Maison de Santé Protestante Bordeaux Bagatelle, Talence, France
INSERM UMR1231 GAD, FHU-TRANSLAD, Université de Bourgogne, Dijon, France
Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA
Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA
Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel
Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel
Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, UK
College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
School of Medicine, University of Queensland, Brisbane, QLD, Australia
White Matter Disease Care, Pediatric Neurology Unit, Dana-Dwak Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
UF Innovation en diagnostic genomique des maladies rares, CHU Dijon Bourgogne, Dijon, France
Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Pediatrics, Peking University First Hospital, Beijing, China
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA
Department of Epilepsy Genetics, Danish Epilepsy Centre Filadelfia, Dianalund, Denmark
Tel Aviv University Medical School, Tel Aviv, Israel
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA
Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada
Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital Frankfurt, and Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany
Service de génétique médicale, CHU Nantes, Nantes, France
Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Section for Medical Genetics, Telemark Hospital, Skien, Norway
Service de Neuropédiatrie, Pôle de Médecine et Spécialités Médicales, CHRU de Lille, Lille, France
Lyon University Hospitals, Departments of Genetics, Lyon, France
University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands
Child and Youth, Randers Regional Hospital, Randers, Denmark
Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA
Stichting Epilepsie Instellingen Nederland, Zwolle, The Netherlands
Section for Medical Genetics, Telemark Hospital, Skien, Norway
Clinical Hospital "Psychiatry", Kyiv, Ukraine
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands
Pediatric Neurology Unit, University Hospitals, Geneva, Switzerland
Service de génétique médicale, CHU Nantes, Nantes, France
Lyon University Hospitals, Departments of Genetics, Lyon, France
Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA
Medical Genetics, St George's University Hospitals NHS FT, Cranmer Tce, London, United Kingdom
Lyon University Hospitals, Departments of Genetics, Lyon, France
Department of Neuroscience, Pharmacology and Child Health, Children's Hospital A. Meyer and University of Florence, Florence, Italy
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA
Department of Neuroscience, Pharmacology and Child Health, Children's Hospital A. Meyer and University of Florence, Florence, Italy
Medigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland
Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital Frankfurt, and Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany
Department of Paediatrics and Child Health, University of Otago Wellington, Wellington, New Zealand
Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada
Stichting Epilepsie Instellingen Nederland, Zwolle, The Netherlands
One Centre of Genetics, Vadodara, India
Neuropaediatric Unit, Shaare Zedek Medical Centre, Hebrew University School of Medicine, Jerusalem, Israel
Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, United Kingdom and Chalfont Centre for Epilepsy, Bucks, UK
Institut de Génétique Médicale, Hopital Jeanne de Flandre, Lille University Hospital, Lille, France
Department of Clinical Genetics and GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Academic Center for Epileptology, Kempenhaege, Department of Neurology, Heeze, The Netherlands
Molecular Genetics Lab, Wolfson Medical Center, Holon, Israel
Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA
Department of Neuroscience, Pharmacology and Child Health, Children's Hospital A. Meyer and University of Florence, Florence, Italy
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA
Department of Pediatrics, Peking University First Hospital, Beijing, China
Issue Date: Feb-2021
metadata.dc.date: 2020-11-04
Publication information: Genetics in Medicine 2021; 23(2): 363-373
Abstract: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants.
URI: https://ahro.austin.org.au/austinjspui/handle/1/25258
DOI: 10.1038/s41436-020-00988-9
ORCID: 0000-0002-2311-2174
PubMed URL: 33144681
Type: Journal Article
Subjects: KIAA2022
NEXMIF
developmental and epileptic encephalopathy
epilepsy
intellectual disability
Appears in Collections:Journal articles

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