RESEARCH ARTICLE A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability Poh Hui Chia1†*, Franklin Lei Zhong1,2†*, Shinsuke Niwa3,4†, Carine Bonnard1, Kagistia Hana Utami5, Ruizhu Zeng5, Hane Lee6,7, Ascia Eskin6,7, Stanley F Nelson6,7, William H Xie1, Samah Al-Tawalbeh8, Mohammad El-Khateeb9, Mohammad Shboul10, Mahmoud A Pouladi5,11, Mohammed Al-Raqad8, Bruno Reversade1,2,12,13* 1Institute of Medical Biology, Immunos, Singapore; 2Institute of Molecular and Cell Biology, Proteos, Singapore; 3Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan; 4Graduate School of Life Sciences, Tohoku University, Sendai, Japan; 5Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore, Singapore; 6Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; 7Department of Human Genetics, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, United States; 8Queen Rania Paediatric Hospital, King Hussein Medical Centre, Royal Medical Services, Amman, Jordan; 9National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan; 10Al-Balqa Applied University, Faculty of Science, Al-Salt, Jordan; 11Department of Medicine, Yong Loo Lin School of *For correspondence: 12
[email protected] Medicine, National University of Singapore, Singapore, Singapore; Department of 13 (PHC); Paediatrics, National University of Singapore, Singapore, Singapore; Medical
[email protected] Genetics Department, Koc¸ University School of Medicine, Istanbul, Turkey (FLZ);
[email protected] (BR) †These authors contributed equally to this work Abstract Calcium/calmodulin-dependent protein kinase II (CAMK2) plays fundamental roles in synaptic plasticity that underlies learning and memory.