Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

Anne O’donnell-Luria , Lynn Pais , Víctor Faundes , Jordan Wood , Abigail Sveden , Victor Luria , Rami Abou Jamra (1) , Andrea Accogli , Kimberly Amburgey , Britt Marie Anderlid (2) , Silvia Azzarello-Burri , Alice Basinger , Claudia S Bianchini (3) , Lynne Bird , Rebecca Buchert , Wilfrid Carré (4) , Sophia Ceulemans , Perrine Charles (5) , Lisa Culliton , Aurora Currò , Florence Demurger (6) , James J. Dowling (7) , Bénédicte Duban-Bedu (8) , Christèle Dubourg (9) , Saga Elise Eiset , Luis Escobar , Alessandra Ferrarini (10) , Tobias B Haack (11) , Mona Hashim , Solveig Heide (12) , Katherine L. Helbig (13) , Ingo Helbig (13) , Raul Heredia , Delphine Héron (14) , Bertrand Isidor (15) , Amy Jonasson , Pascal Joset , Boris Keren (14) , Fernando Kok , Hester Kroes , Alinoë Lavillaureix , Xin Lu (16) , Saskia Maas , Gustavo H.B. Maegawa , Carlo L.M. Marcelis , Paul Mark , Marcelo Masruha , Heather Mclaughlin , Kirsty Mcwalter , Esther Melchinger , Saadet Mercimek-Andrews , Caroline Nava (14) , Manuela Pendziwiat , Richard E. Person (17) , Gian Paolo Ramelli , Luiza L.P. Ramos , Anita Rauch (18) , Caitlin Reavey , Alessandra Renieri (19) , Angelika Riess , Amarilis Sanchez-Valle , Shifteh Sattar , Carol Saunders , Niklas Schwarz , Thomas Smol (20) , Myriam Srour , Katharina Steindl , Steffen Syrbe , Jenny Taylor (21) , Aida Telegrafi (22) , Isabelle Thiffault , Doris Trauner , Helio van Der Linden , Silvana van Koningsbruggen (23) , Laurent Villard (24) , Ida Vogel (25) , Yvonne Weber , Ingrid Wentzensen (22) , Elysa Widjaja , Jaroslav Zak , Samantha Baxter , Lance H Rodan (26) , Jeremy Mcrae , Stephen Clayton , Tomas Fitzgerald (27) , Joanna Kaplanis , Elena Prigmore , Diana Rajan , Alejandro Sifrim , Stuart Aitken , Nadia Akawi , Mohsan S Alvi (28) , Kirsty Ambridge , Daniel Barrett , Tanya Bayzetinova , Philip D Jones (29) , Wendy Jones , Daniel King (30) , Netravathi Krishnappa , Laura Mason , Tarjinder Singh , Adrian Tivey , Munaza Ahmed (31) , Uruj Anjum , Hayley Archer , Ruth Armstrong (32) , Jana Awada , Meena Balasubramanian (33) , Siddharth Banka (34) , Diana Baralle (35) , Angela Barnicoat (36) , Paul Batstone , David Baty , Chris Bennett (37) , Jonathan Berg (38) , Birgitta Bernhard , A. Paul Bevan , Maria Bitner-Glindzicz (36) , Edward Blair (39) , Moira Blyth , David Bohanna , Louise Bourdon , David Bourn , Lisa Bradley , Angela F. Brady (40) , Simon Brent , Carole Brewer (41) , Kate Brunstrom , David Bunyan , John Burn , Natalie Canham , Bruce Castle (42) , Kate Chandler , Elena Chatzimichali , Deirdre Cilliers , Angus Clarke , Susan Clasper , Jill Clayton-Smith (43) , Virginia Clowes , Andrea Coates , Trevor Cole (44) , Irina Colgiu , Amanda Collins (45) , Morag Collinson , Fiona Connell (46) , Nicola Cooper , Helen Cox , Lara Cresswell (47) , Gareth Cross , Yanick Crow (48) , Mariella D’alessandro , Tabib Dabir (49) , Rosemarie Davidson (50) , Sally Davies (51) , Dylan de Vries , John Dean (52) , Charu Deshpande (46) , Gemma Devlin , Abhijit Dixit (53) , Angus Dobbie , Alan Donaldson (54) , Dian Donnai (55) , Deirdre Donnelly , Carina Donnelly , Angela Douglas , Sofia Douzgou , Alexis Duncan , Jacqueline Eason (56) , Sian Ellard (57) , Ian Ellis (58) , Frances Elmslie (59) , Karenza Evans , Sarah Everest , Tina Fendick , Richard Fisher (60) , Frances Flinter , Nicola Foulds (45) , Andrew Fry (61) , Alan Fryer (62) , Carol Gardiner , Lorraine Gaunt (63) , Neeti Ghali (64) , Richard Gibbons , Harinder Gill , Judith Goodship (65) , David Goudie (66) , Emma Gray , Andrew Green (67) , Philip Greene , Lynn Greenhalgh , Susan Gribble , Rachel Harrison (68) , Lucy Harrison , Victoria Harrison , Rose Hawkins , Liu He (69) , Stephen Hellens , Alex Henderson (70) , Sarah Hewitt , Lucy Hildyard , Emma Hobson , Simon Holden , Muriel Holder (71) , Susan Holder , Georgina Hollingsworth , Tessa Homfray , Mervyn Humphreys , Jane Hurst , Ben Hutton , Stuart Ingram , Melita Irving , Lily Islam , Andrew Jackson (72) , Joanna Jarvis , Lucy Jenkins , Diana Johnson (73) , Elizabeth Jones , Dragana Josifova (74) , Shelagh Joss (75) , Beckie Kaemba , Sandra Kazembe , Rosemary Kelsell , Bronwyn Kerr (34) , Helen Kingston (76) , Usha Kini (77) , Esther Kinning , Gail Kirby , Claire Kirk , Emma Kivuva , Alison Kraus , Dhavendra Kumar , V. Kumar (78) , Katherine Lachlan (79) , Wayne Lam (45) , Anne Lampe (80) , Caroline Langman , Melissa Lees (81) , Derek Lim (82) , Cheryl Longman , Gordon Lowther , Sally Lynch , Alex Magee , Eddy Maher , Alison Male , Sahar Mansour (83) , Karen Marks , Katherine R. Martin (84) , Una Maye , Emma Mccann (85) , Vivienne Mcconnell , Meriel Mcentagart (81) , Ruth Mcgowan (65) , Kirsten Mckay , Shane Mckee (76) , Dominic Mcmullan (86) , Susan Mcnerlan , Catherine Mcwilliam , Sarju Mehta , Kay Metcalfe (87) , Anna Middleton (88) , Zosia Miedzybrodzka , Emma Miles , Shehla Mohammed (89) , Tara Montgomery (90) , David Moore (91) , Sian M. Morgan (92) , Jenny Morton (93) , Hood Mugalaasi , Victoria Murday , Helen Murphy (94) , Swati Naik , Andrea Nemeth (95) , Louise Nevitt , Ruth Newbury-Ecob (96) , Andrew Norman , Rosie O’shea , Caroline Ogilvie , Kai-Ren Ong (97) , Soo-Mi Park , Chirag Patel (98) , Joan Paterson (99) , Stewart Payne , Daniel Perrett , Julie Phipps , Daniela T. Pilz (100) , Martin Pollard , Caroline Pottinger , Joanna Poulton , Norman Pratt , Katrina Prescott (101) , Sue Price (102) , Abigail Pridham , Annie Procter , Hellen Purnell , Oliver Quarrell , Nicola Ragge (68) , Raheleh Rahbari (103) , Josh Randall , Julia Rankin (104) , Lucy Raymond , Debbie Rice , Leema Robert (105) , Eileen Roberts , Jonathan Roberts (106) , Paul Roberts (107) , Gillian Roberts , Alison Ross , Elisabeth Rosser , Anand Saggar (108) , Shalaka Samant , Julian Sampson (109) , Richard Sandford (110) , Ajoy Sarkar (111) , Susann Schweiger , Richard Scott (112) , Ingrid Scurr , Ann Selby , Anneke Seller , Cheryl Sequeira , Nora Shannon (113) , Saba Sharif (114) , Charles Shaw-Smith (115) , Emma Shearing , Debbie Shears (116) , Eamonn Sheridan (117) , Ingrid Simonic (118) , Roldan Singzon , Zara Skitt , Audrey Smith , Kath Smith (33) , Sarah Smithson (96) , Linda Sneddon , Miranda Splitt (119) , Miranda Squires , Fiona Stewart (120) , Helen Stewart , Volker Straub (121) , Mohnish Suri (122) , Vivienne Sutton , Ganesh Jawahar Swaminathan , Elizabeth Sweeney (123) , Kate Tatton-Brown , Cat Taylor , Rohan Taylor , Mark Tein (124) , I. Karen Temple (42) , Jenny Thomson , Marc Tischkowitz (125) , Susan Tomkins , Audrey Torokwa , Becky Treacy (126) , Claire Turner , Peter Turnpenny , Carolyn Tysoe , Anthony A Vandersteen (127) , Vinod Varghese , Pradeep Vasudevan (47) , Parthiban Vijayarangakannan , Julie Vogt (82) , Emma Wakeling (128) , Sarah Wallwark , Jonathon Waters , Astrid Weber , Diana Wellesley , Margo Whiteford (129) , Sara Widaa , Sarah Wilcox , Emily Wilkinson , Denise Williams (130) , Nicola Williams , Louise Wilson , Geoff Woods , Christopher Wragg , Michael Wright , Laura Yates , Michael Yau , Chris Nellåker , Michael Parker (131) , Helen Firth (132) , Caroline Wright , David Fitzpatrick (45) , Jeffrey Barrett (103) , Matthew E. Hurles (115)

1 Department of Medicine 1
2 Center for Medical Genetics
3 ISTC, CNR - Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche
4 SBR - Station biologique de Roscoff [Roscoff]
5 Service de Neurologie [CHU Pitié-Salpêtrière]
6 Génétique médicale [Centre Hospitalier de Vannes]
7 Department of Pediatrics
8 Centre de Génétique Chromosomique [Hôpital Saint Vincent de Paul]
9 IGDR - Institut de Génétique et Développement de Rennes
10 Service de génétique médicale
11 Institute of Human Genetics
12 GRC - Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme
13 CHOP - Children’s Hospital of Philadelphia
14 Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière]
15 Service de Génétique Médicale
16 Department of Public Health Sciences
17 Department of Molecular and Human Genetics
18 Institute of Medical Genetics
19 UNICAM - Università degli Studi di Camerino = University of Camerino
20 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
21 University of Oxford
22 GeneDx [Gaithersburg, MD, USA]
23 Department of Clinical Genetics (Academic Medical Center, University of Amsterdam)
24 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
25 Department of Clinical Genetics
26 Boston Children's Hospital
27 Wellcome Trust Genome Campus
28 IBME - Institute of Biomedical Engineering [Oxford]
29 Climatic Research Unit
30 Imperial College London
31 St Mary's Hospital
32 East Anglian Medical Genetics Service, Cytogenetics Laboratory, Addenbrooke's Hospital
33 Sheffield Children's NHS Foundation Trust
34 Regional Genetic Service, St Mary's Hospital, Manchester
35 Genetics
36 GOSH - Great Ormond Street Hospital for Children [London]
37 Yorkshire Regional Clinical Genetics Service
38 School of Medicine - Molecular and Clinical Medicine [Dundee, UK]
39 Department of Clinical Genetics, Oxford Regional Genetics Service
40 North West Thames Regional Genetics
41 Department of Clinical Genetics
42 Wessex Clinical Genetics Service
43 MFT - Manchester University NHS Foundation Trust
44 West Midlands Regional Genetics Service
45 Our Lady's hospital for Sick Children
46 Guy's Hospital [London]
47 University Hospitals Leicester
48 University of Edinburgh
49 Belfast City Hospital
50 Ferguson-Smith Centre for Clinical Genetics
51 Institute of Medical Genetics, Heath Park, Cardiff
52 The London Clinic
53 Nottingham City Hospital
54 Clinical Genetics Department
55 Department of Genetic Medicine
56 Nottingham Clinical Genetics Service
57 Royal Devon and Exeter Foundation Trust
58 Histopathology
59 St. George's Hospital
60 Teesside Genetics Unit
61 Kansas State University
62 Liverpool Women's NHS Foundation Trust
63 Department of Medical Genetics
64 North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow
65 Department of Clinical Genetics
66 Ninewells Hospital and Medical School [Dundee]
67 ACoRD - Academic Centre on Rare Diseases
68 Oxford Brookes University
69 Institute of medicinal plant development
70 Newcastle Upon Tyne Hospitals NHS Trust
71 Service d'explorations fonctionnelles respiratoires [Lille]
72 Department of Computer Science - Trinity College Dublin
73 Department of Clinical Genetics (Sheffield Children’s NHS Foundation Trust)
74 Division of Medical & Molecular Genetics
75 NHSGGC - NHS Greater Glasgow & Clyde [Glasgow]
76 Institute of Medical Genetics
77 Department of Clinical Genetics [Churchill Hospital]
78 Weizmann Institute of Science [Rehovot, Israël]
79 Southampton General Hospital
80 Department of Clinical Genetics
81 Head of the Department of Medical Genetics
82 University of Birmingham [Birmingham]
83 SW Thames Regional Genetics Service, St George’s University of London, London
84 IC UM3 (UMR 8104 / U1016) - Institut Cochin
85 All Wales Medical Genetics Services
86 Clinical Genetics Department
87 Central Manchester University Hospitals NHS Foundation Trust
88 UNT - University of North Texas
89 Clinical Genetics
90 Northern Genetics Service
91 United Kingdom Met Office [Exeter]
92 Institute of Medical Genetics (University Hospital of Wales)
93 West Midlands Regional Genetics Laboratory and Clinical Genetics Unit
94 Laboratory of Molecular Genetics
95 Department of Genetics, Cell- and Immunobiology
96 University Hospitals Bristol
97 West Midlands Regional Genetics Service
98 MKT - Marketing
99 Department of Clinical Genetics
100 West of Scotland Genetics Service (Queen Elizabeth University Hospital)
101 Department of Clnical Genetics, Chapel Allerton Hospital
102 Department of Clinical Genetics, Northampton General Hospital, Northampton
103 The Wellcome Trust Sanger Institute [Cambridge]
104 Clinical Genetics
105 Guy's and St Thomas' Hospital [London]
106 School of Computer Science
107 University Hospital Southampton
108 Clinical Genetics Unit
109 Medical Genetics
110 Research and Development
111 Nottingham Regional Genetics Service [Nottingham, UK]
112 University of St Andrews [Scotland]
113 Clinical Genetics Service
114 West Midlands Regional Genetics Unit
115 Department of Neurology
116 Oxford University Hospitals NHS Trust
117 St James's University Hospital
118 Addenbrooke's Hospital
119 Institute of Human Genetics, Newcastle
120 Division of Biological Stress Response [Amsterdam, The Netherlands]
121 Department of Neurology
122 Clinical Genetics Service
123 Johns Hopkins Bloomberg School of Public Health [Baltimore]
124 Clinical Genetics
125 Department of Genetics
126 Molecular Genetics
127 IWK Health Centre
128 North West london hospitals NHS Trust
129 Department of Clinical Genetics (Queen Elizabeth University Hospital, Glasgow)
130 Birmingham women's hospital, Birmingham
131 Ethox Centre, Department of Public Health and Primary Health Care
132 Department of Clinical Genetics

Keywords: global developmental delay; epileptic encephalopathy; epilepsy; autism; KMT2E; H3K4 methylation; intellectual disability; neurodevelopmental disorder

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Genetics; Life Sciences [q-bio]; Genetics; Human genetics

Anne O’donnell-Luria, Lynn Pais, Víctor Faundes, Jordan Wood, Abigail Sveden, et al.. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy. American Journal of Human Genetics, 2019, 104 (6), pp.1210-1222. ⟨10.1016/j.ajhg.2019.03.021⟩. ⟨hal-02417518⟩