De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability - Université de Nantes Accéder directement au contenu
Article Dans Une Revue American Journal of Human Genetics Année : 2017

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability

Sébastien Küry (1) , Geeske M van Woerden (2, 3) , Thomas Besnard (1) , Martina Proietti Onori (2, 3) , Xénia Latypova (1) , Meghan C Towne (4, 5) , Megan T Cho (6) , Trine E Prescott (7) , Melissa A Ploeg (2, 3) , Stephan J. Sanders (8) , Holly A.F. Stessman (9, 10) , Aurora Pujol (11, 12, 13) , Ben Distel (2, 3, 14) , Laurie A Robak (15) , Jonathan A. Bernstein (16) , Anne-Sophie Denommé-Pichon (17, 18) , Gaëtan Lesca (19, 20) , Elizabeth A Sellars (21) , Jonathan Berg (22) , Wilfrid Carré (23) , Øyvind Løvold Busk (7) , Bregje W.M. van Bon (24) , Jeff L Waugh (25) , Matthew A. Deardorff (26) , George E Hoganson (27) , Katherine B Bosanko (21) , Diana S. Johnson (28) , Tabib Dabir (29) , Øystein Lunde Holla (7) , Ajoy Sarkar (30) , Kristian Tveten (7) , Julitta de Bellescize (31) , Geir J. Braathen (7) , Paulien A Terhal (32) , Dorothy K Grange (33) , Arie van Haeringen (34) , Christina Lam (35) , Ghayda Mirzaa (35, 36) , Jennifer Burton (27) , Elizabeth J. Bhoj (37, 38) , Jessica Douglas (4) , Avni B. Santani (39, 40) , Addie I. Nesbitt (39) , Katherine L. Helbig (41, 42) , Marisa V. Andrews (33) , Amber Begtrup (6) , Sha Tang (41) , Koen L.I. van Gassen (32) , Jane Juusola (6) , Kimberly Foss (36) , Gregory M. Enns (16) , Ute Moog (43) , Katrin Hinderhofer (43) , Nagarajan Paramasivam (44) , Sharyn Lincoln (4) , Brandon H. Kusako (4) , Pierre Lindenbaum (45) , Eric Charpentier (45) , Catherine B. Nowak (4) , Elouan Cherot (23) , Thomas Simonet (31) , Claudia A.L. Ruivenkamp (34) , Sihoun Hahn (35) , Catherine A. Brownstein (4, 5) , Fan Xia (15, 46) , Sébastien Schmitt (1) , Wallid Deb (1) , Dominique Bonneau (17, 18) , Mathilde Nizon (1) , Delphine Quinquis (1) , Jamel Chelly (47, 48, 49) , Gabrielle Rudolf (48, 49, 50) , Damien Sanlaville (19, 20) , Philippe Parent (51) , Brigitte Gilbert-Dussardier (52) , Annick Toutain (53) , Vernon R. Sutton (46) , Jenny Thies (35) , Lisenka E.L.M. Peart-Vissers (24) , Pierre Boisseau (1) , Marie Vincent (1) , Andreas M. Grabrucker (54, 55) , Christèle Dubourg (23) , Undiagnosed Diseases Network (4) , Wen-Hann Tan (4) , Nienke E. Verbeek (32) , Martin Granzow (43) , Gijs W.E. Santen (34) , Jay Shendure (9, 56) , Bertrand Isidor (1) , Laurent Pasquier (57) , Richard Redon (45) , Yaping Yang (15, 46) , Matthew W. State (58) , Tjitske Kleefstra (24) , Benjamin Cogné (1) , Gem Hugo (59) , Deciphering Developmental Disorders Study (60) , Slavé Petrovski (61) , Kyle Retterer (6) , Evan E. Eichler (9, 56) , Jill A. Rosenfeld (15) , Pankaj B. Agrawal (4, 5, 62) , Stéphane Bézieau (63, 1) , Sylvie Odent (57) , Ype Elgersma (2, 3) , Sandra Mercier (1)
1 Service de génétique médicale [CHU Nantes]
2 Department of Neuroscience [Rotterdam, the Netherlands]
3 ENCORE - Expertise Center for Neurodevelopmental Disorders [Rotterdam, the Netherlands]
4 Genomics Program and Division of Genetics [Boston, USA]
5 The Manton Center for Orphan Disease Research - Gene Discovery Core [Boston, MA, USA]
6 GeneDx [Gaithersburg, MD, USA]
7 Department of Medical Genetics [Skien, Norway]
8 Department of Psychiatry [San Francisco, CA, USA]
9 GS - Department of Genome Sciences [Seattle]
10 Department of Pharmacology [Omaha, NE, USA]
11 Neurometabolic Diseases Laboratory [Barcelona, Spain]
12 CIBERER - Centre for Biomedical Research on Rare Diseases [Barcelona, Spain]
13 ICREA - Institució Catalana de Recerca i Estudis Avançats
14 Academic Medical Center - Department of Medical Biochemistry [Amsterdam, the Netherlands]
15 Department of Molecular and Human Genetics [Houston, USA]
16 Department of Pediatrics [Stanford]
17 Département de Biochimie et Génétique [Angers]
18 BNMI - Biologie Neurovasculaire et Mitochondriale Intégrée
19 Centre de Référence des Anomalies du Développement - Service de Génétique [HCL, Lyon]
20 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
21 Section of Genetics and Metabolism [Little Rock, AR, USA]
22 School of Medicine - Molecular and Clinical Medicine [Dundee, UK]
23 Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes]
24 Department of Human Genetics [Nijmegen]
25 Department of Neurology [Boston]
26 Division of Genetics - Department of Pediatrics [Philadelphia, PA, USA]
27 College of Medicine - Department of Pediatrics [Chicago, IL, USA]
28 Sheffield Children's NHS Foundation Trust
29 Northern Ireland Regional Genetics Centre [Belfast, UK]
30 Nottingham Regional Genetics Service [Nottingham, UK]
31 Département d'Epilepsie, Sommeil et Neurophysiologie Pédiatrique [HCL, Lyon]
32 Department of Genetics [Utrecht, the Netherlands]
33 Division of Genetics and Genomic Medicine - Department of Pediatrics [Saint Louis, MO, USA]
34 Department of Clinical Genetics [Leiden, the Netherlands]
35 Department of Pediatrics [Seattle, WA, USA]
36 Center for Integrative Brain Research [Seattle, WA, USA]
37 The Center for Applied Genomics [Philadelphia, PA, USA]
38 Division of Human Genetics [Philadelphia, PA, USA]
39 Department of Pathology and Laboratory Medicine [Philadelphia, PA, USA]
40 Perelman School of Medicine - Department of Pathology and Laboratory Medicine [Philadelphia, PA, USA]
41 Division of Clinical Genomics [Aliso Viejo, CA, USA]
42 Division of Neurology [Philadelphia, PA, USA]
43 Institute of Human Genetics [Heidelberg, Germany]
44 University of Heidelberg, Medical Faculty
45 ITX - ITX - unité de recherche de l'institut du thorax
46 Baylor College of Medecine
47 Laboratoire de Diagnostic Génétique [CHU Strasbourg]
48 FMTS - Fédération de Médecine Translationnelle de Strasbourg
49 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
50 Service de Neurologie [CHU Strasbourg]
51 Département de génétique médicale en pédiatrie [CHRU Brest]
52 Service de Génétique [CHU Poitiers]
53 Service de Génétique [CHRU Tours]
54 Department of Biological Sciences [Limerick, Ireland]
55 Bernal Institute [Limerick, Ireland]
56 Howard Hughes Medical Institute [Seattle]
57 IGDR - Institut de Génétique et Développement de Rennes
58 Department of Psychiatry [San Francisco, CA, USA]
59 Service de génétique clinique [Rennes]
60 The Wellcome Trust Sanger Institute [Cambridge]
61 Department of Medicine [Melbourne, Australia]
62 Division of Newborn Medicine [Boston, MA, USA]
63 CRCINA-ÉQUIPE 1 - Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications
Ute Moog
  • Fonction : Auteur
  • PersonId : 887755
Annick Toutain
Tjitske Kleefstra
  • Fonction : Auteur
  • PersonId : 916703

Résumé

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway.

Domaines

Cancer
Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée
Loading...

Dates et versions

inserm-01813739 , version 1 (12-06-2018)

Identifiants

Citer

Sébastien Küry, Geeske M van Woerden, Thomas Besnard, Martina Proietti Onori, Xénia Latypova, et al.. De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. American Journal of Human Genetics, 2017, 101 (5), pp.768 - 788. ⟨10.1016/j.ajhg.2017.10.003⟩. ⟨inserm-01813739⟩
398 Consultations
3 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More