@article{09d44205dcdf4acea9592d02fd2b56db,
title = "Recurrent de novo MAPK8IP3 variants cause neurological phenotypes",
abstract = "c-Jun-amino-terminal kinase-interacting protein 3 (JIP3), encoded by MAPK8IP3, is an adaptor protein of the kinesin-1 complex and essential for axonal transport in neurons. However, an association between MAPK8IP3 variants and human disease has not been established. We identified 5 individuals from four families with recurrent de novo variants c.1732C>T (p.Arg578Cys) and c.3436C>T (p.Arg1146Cys) in MAPK8IP3. The core phenotype includes spastic diplegia, intellectual disability, cerebral atrophy, and corpus callosum hypoplasia. Zebrafish embryos overexpressing human mutant JIP3 showed axon varicosities of the posterior lateral line nerve, suggesting an adverse effect on the developing axons. Our results suggest that MAPK8IP3 variants cause a neurodevelopmental disease. ANN NEUROL 2019;85:927–933.",
author = "Shinya Iwasawa and Kumiko Yanagi and Atsuo Kikuchi and Yasuko Kobayashi and Kazuhiro Haginoya and Hiroshi Matsumoto and Kenji Kurosawa and Masayuki Ochiai and Yasunari Sakai and Atsushi Fujita and Noriko Miyake and Tetsuya Niihori and Matsuyuki Shirota and Ryo Funayama and Shigeaki Nonoyama and Shouichi Ohga and Hiroshi Kawame and Keiko Nakayama and Yoko Aoki and Naomichi Matsumoto and Tadashi Kaname and Yoichi Matsubara and Wataru Shoji and Shigeo Kure",
note = "Funding Information: The authors thank the patients and families who participated in this study. We thank Dr. Mari Minatogawa for clinical supports. We also thank Yoko Chiba, Kumi Ito, Miyuki Tsuda, Mami Kikuchi, Makiko Nakagawa, Yoko Tateda, Kiyotaka Kuroda, Keiko Hayashi, and Manami Iso for providing technical assistance. We also acknowledge the support from the Biomedical Research Core of the Tohoku University Graduate School of Medicine and the Biomedical Research Unit of Tohoku University Hospital. Funding Information: From the 1Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan; 2National Center for Child Health and Development, Tokyo, Japan;3Department of Pediatrics, National Hospital Organization Sendai-Nishitaga Hospital, Sendai, Japan; 4Department of Pediatric Neurology, Takuto Rehabilitation Center for Children, Sendai, Japan; 5Department of Pediatric Neurology, Miyagi Children{\textquoteright}s Hospital, Sendai, Japan; 6Department of Pediatrics, National Defense Medical College, Saitama, Japan; 7Division of Medical Genetics, Kanagawa Children{\textquoteright}s Medical Center, Yokohama, Japan; 8Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 9Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 10Department of Medical Genetics, Tohoku University Graduate School of Medicine, Sendai, Japan; 11Division of Interdisciplinary Medical Sciences, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 12Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 13Tohoku Medical Megabank organization, Tohoku University, Sendai, Japan; and 14Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan Address correspondence to Dr Atsuo Kikuchi, Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. E-mail: akikuchi-thk@umin.ac.jp; or Dr Shigeo Kure, Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. E-mail: kure@med.tohoku.ac.jp Additional supporting information can be found in the online version of this article. Funding Information: This research was supported by the Japanese Agency for Medical Research and Development (AMED) through grant numbers JP17ek0109151 (Initiative on Rare and Undiagnosed Diseases [IRUD] to S.K.), JP18ek0109301 (IRUD to Na.M. and Y.M.), JP18ek0109280 (to Na.M.), JP18kk0205001 (to Na.M.), JP18ek0109348 (to Na.M.), and JP18ek0109288 (IRUD beyond to W.S.) and by Japan Society for the Promotion of Science (JSPS) grant numbers JP17H01539 (to Na.M.). This work was also supported by grants from Novartis (to A.K.).",
year = "2019",
month = jun,
doi = "10.1002/ana.25481",
language = "English",
volume = "85",
pages = "927--933",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "6",
}