Human Mutation
Mutation Update for K abuki syndrome genes KMT2D and KDM6A and further delineation of X-linked Kabuki syndrome subtype 2
For Peer Review Journal: Human Mutation
Manuscript ID humu 2015 0531.R1
Wiley Manuscript type: Mutation Update
Date Submitted by the Author: 20 May 2016
Complete List of Authors: Bögershausen, Nina; University Medical Center Goettingen, Institute of Human Genetics; University of Cologne, Institute of Human Genetics Gatinois, Vincent; CHU Montpellier, Laboratory of Rare and Autoinflammatory Diseases; University of Montpellier; INSERM UMR1183 Riehmer, Vera; University of Cologne, Institute of Human Genetics Kayserili, Hülya; Koç University School of Medicine (KUSOM) , Medical Genetics Department Becker, Jutta; University of Cologne, Institute of Human Genetics Thoenes, Michaela; University of Cologne, Institute of Human Genetics Simsek Kiper, Pelin; Hacettepe University, Ihsan Dogramaci Children's Hospital BARAT HOUARI, MOUNA; CHRU de Montpellier, Laboratoire de génétique des maladies rares et autoinflammatoires ; INSERM UMR1183, Elcioglu, Nursel; Marmara University Medical Faculty, Department of Pediatric Genetics Wieczorek, Dagmar; Heinrich Heine Universitat Dusseldorf Medizinische Fakultat, Institute of Human Genetics Tinschert, Sigrid; Medical University Innsbruck, Division of Human Genetics; Technische Universität Dresden, Institute for Clinical Genetics Sarrabay, Guillaume; Centre Hospitalier Regional Universitaire de Montpellier, Laboratory of Rare and Autoinflammatory Diseases; University of Montpellier; INSERM UMR1183 Strom, Tim; Helmholtz Zentrum München, Institute of Human Genetics; Technische Universität München, Institute of Human Genetics FABRE, Aurélie; CHRU de Montpellier, GENETIC Baynam, Gareth; University of Western Australia, Genetic Services of Western Australia; Western Australian Register of Developmental Anomalies; Telethon Kids Institute; University of Western Australia, School of Paediatrics and Child Health Sanchez, Elodie; INSERM UMR1183 Nürnberg, Gudrun; University of Cologne, Cologne Center for Genomics Altunoglu, Umut; Istanbul Medical Faculty, Istanbul University, Department of Medical Genetics Capri, Yline; APHP Robert DEBRE University Hospital, Paris VII University, Department of Genetics Isidor, Bertrand; Nantes University Hospital, Department of Genetics
John Wiley & Sons, Inc. Page 1 of 119 Human Mutation
1 2 3 4 Lacombe, Didier; Centre Hospitalier Universitaire de Bordeaux, INSERM 5 U1211, Bordeaux University, Department of Medical Genetics Corsini, Carole; University of Montpellier; INSERM UMR1183; CHU 6 Montpellier, Department of Medical Genetics, Reference Center for 7 Developmental Abnormalities 8 Cormier Daire, Valerie; Université Paris Descartes Sorbonne Paris Cité, 9 Institut Imagine, INSERM U1163, Paris Descartes Sorbonne Paris Cité 10 University; Hopital universitaire Necker Enfants malades, Service de 11 Génétique, Assistance Publique Hôpitaux de Paris 12 Sanlaville, Damien; Hospices Civils Lyon, HCL Genetic department, INSERM 13 U1028 CNRS UMR 5292, UCBL1, CRNL, GENDEV Team Giuliano, Fabienne; CHU Hôpital l'Archet 2, Service de Génétique Médicale 14 Le Quan Sang, Kim Hanh; Université Paris Descartes Sorbonne Paris Cité, 15 Institut Imagine, INSERM U1163, Hôpital Necker Enfants Malades 16 Kayirangwa, Honorine; Université Paris Descartes Sorbonne Paris Cité, 17 Institut Imagine, INSERM U1163, Hôpital Necker Enfants Malades 18 ForNürnberg, Peer Peter; Cologne Review Center for Genomics (CCG), University of 19 Cologne 20 Meitinger, Thomas; Helmholtz Zentrum München, Institute of Human 21 Genetics; Technische Universität München, Institute of Human Genetics Boduroğlu, Koray; Hacettepe University School of Medicine Ihsan 22 Dogramaci Children's Hospital, Department of Pediatrics Clinical Genetics 23 Section 24 Zoll, Barbara; University Medical Center Goettingen, Institut of Human 25 Genetics 26 LYONNET, Stanislas; Université Paris Descartes Sorbonne Paris Cité, 27 Institut Imagine, INSERM U1163; Hopital universitaire Necker Enfants 28 malades, Service de Génétique, Assistance Publique Hôpitaux de Paris Tzschach, Andreas; Faculty of Medicine Carl Gustav Carus, Technische 29 Universität Dresden, Institute for Clinical Genetics 30 Verloes, Alain; APHP Robert DEBRE University Hospital, Paris VII 31 University, Department of Genetics 32 DiDonato, Nataliya; Faculty of Medicine Carl Gustav Carus, Technische 33 Universität Dresden, Institute for Clinical Genetics 34 Touitou, Isabelle; Centre Hospitalier Regional Universitaire de Montpellier, 35 Laboratory of Rare and Autoinflammatory Diseases; University of 36 Montpellier; INSERM UMR1183 Netzer, Christian; University of Cologne, Institute of Human Genetics; 37 Li, Yun; University of Cologne, Institute of Human Genetics; University 38 Medical Center Goettingen, Institute of Human Genetics 39 Geneviève, David; University of Montpellier; INSERM UMR1183; CHU de 40 Montpellier, Département de Génétique médicale, Reference Center for 41 Developmental Abnormalities 42 Yigit, Gokhan; University Medical Center Goettingen, Institute of Human 43 Genetics; University of Cologne, Institute of Human Genetics 44 Wollnik, Bernd; University Medical Center Goettingen, Institute of Medical Genetics; University of Cologne, Institute of Human Genetics 45 46 Key Words: Kabuki Syndrome, KMT2D, MLL2, KDM6A, UTX, UTY, Mutation 47 48 49 50 51 52 53 54 55 56 57 58 59 60 John Wiley & Sons, Inc. Human Mutation Page 2 of 119
1 2 3 Mutation Update for Kabuki syndrome genes KMT2D and KDM6A and further delineation 4 5 of X-linked Kabuki syndrome subtype 2 6
7 8 Nina Bögershausen 1, Vincent Gatinois 2,3,4 , Vera Riehmer 5, Hülya Kayserili 6, Jutta Becker 5, 9 5 7 2,4 8 10 Michaela Thoenes , Pelin Özlem Simsek Kiper , Mouna Barat Houari , Nursel H. Elcioglu , 11 Dagmar Wieczorek 9, Sigrid Tinschert 10,11 , Guillaume Sarrabay 2,3,4 , Tim M. Strom 12,13, Aurélie 12 13 Fabre 2, Gareth Baynam 14,15,16,17, Elodie Sanchez 4, Gudrun Nürnberg 18, Umut Altunoglu 19, Yline 14 20 21 22 3,4,23 24,25 15 Capri , Bertrand Isidor , Didier Lacombe , Carole Corsini Valérie Cormier Daire , 16 Damien Sanlaville 26, Fabienne Giuliano 27, Kim Hanh Le Quan Sang 24, Honorine Kayirangwa 24, 17 18 Peter Nürnberg 18, ThomasFor MeitingerPeer12,13, KorayReview Boduroglu 7, Barbara Zoll 1, Stanislas 19 24,25 10 20 10 2,3,4 20 Lyonnet , Andreas Tzschach , Alain Verloes , Nataliya Di Donato , Isabelle Touitou , 21 Christian Netzer 5, Yun Li 1, David Geneviève 3,4,23, Gökhan Yigit 1, and Bernd Wollnik 1 22 23 24 1Institute of Human Genetics, University Medical Center Goettingen, Goettingen, Germany; 2Laboratory of 25 3 26 Rare and Autoinflammatory Diseases, CHU Montpellier, Montpellier, France; University of Montpellier, 27 Montpellier, France; 4INSERM UMR1183, Montpellier, France; 5Institute of Human Genetics, University of 28 6 29 Cologne, Cologne, Germany; Medical Genetics Department, Koç University School of Medicine 30 (KUSOM) İstanbul, Turkey; 7Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University 31 8 32 Medical Faculty, Ankara, Turkey; Department of Pediatric Genetics, Marmara University Medical Faculty, 33 Istanbul, Turkey; 9Institute of Human Genetics, University of Duesseldorf, Duesseldorf, Germany; 34 10 35 Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 36 Germany; 11 Zentrum für Humangenetik, Medizinische Universität Innsbruck, Austria; 12Institute of Human 37 13 38 Genetics, Technische Universität München, Munich, Germany; Institute of Human Genetics, Helmholtz 39 Zentrum München, Neuherberg, Germany; 14Genetic Services of Western Australia, Princess Margaret 40 15 41 and King Edward Memorial Hospitals, Perth, Australia; Western Australian Register of Developmental 42 Anomalies, Perth Australia; 16Telethon Kids Institute, Perth Australia; 17School of Paediatrics and Child 43 18 44 Health, University of Western Australia, Perth, Australia; Cologne Center for Genomics, University of 45 Cologne, Cologne, Germany; 19Department of Medical Genetics, Istanbul Medical Faculty, Istanbul 46 University, Istanbul, Turkey; 20 Department of Genetics, APHP Robert DEBRE University Hospital, Paris 47 48 VII University, Denis Diderot Medical School, Paris, France; 21 Department of Genetics, Nantes University 49 22 Hospital, Nantes, France; CHU Bordeaux, INSERM U1211, Bordeaux University, Department of Medical 50 51 Genetics, Bordeaux, France; 23Department of Medical Genetics, Reference Center for Developmental 52 24 Abnormalities, CHU, Montpellier, France; Institut Imagine, INSERM U1163, Paris Descartes Sorbonne 53 54 Paris Cité University, Paris, France; 25Service de Génétique, Hôpital Universitaire Necker Enfants 55 Malades, Assistance Publique Hôpitaux de Paris, Paris, France; 26HCL Genetic department, INSERM 56 27 57 U1028 CNRS UMR 5292, UCBL1, CRNL, GENDEV Team, Lyon, France; Department of Medical 58 Genetics, l'Archet II Hospital, Nice, France. 59 60 John Wiley & Sons, Inc. Page 3 of 119 Human Mutation
2 1 2 3 Grant numbers: German Federal Ministry of Education and Research (BMBF), grant number 4 5 01GM1211A (E RARE network CRANIRARE 2) and French Ministry of Health (Programme 6 7 Hospitalier de Recherche Clinique national AOM 07 090). 8 9 10 Corresponding author: Prof. Bernd Wollnik, MD 11 Institute of Human Genetics 12 13 University Medical Center Göttingen 14 15 Heinrich Düker Weg 12, 37073 Göttingen, Germany 16 Tel: +49 551 39 7590 Fax: +49 551 39 9303 17 18 For PeerEMail: [email protected]