Recurrent de novo MAPK8IP3 variants cause neurological phenotypes

Shinya Iwasawa, Kumiko Yanagi, Atsuo Kikuchi, Yasuko Kobayashi, Kazuhiro Haginoya, Hiroshi Matsumoto, Kenji Kurosawa, Masayuki Ochiai, Yasunari Sakai, Atsushi Fujita, Noriko Miyake, Tetsuya Niihori, Matsuyuki Shirota, Ryo Funayama, Shigeaki Nonoyama, Shouichi Ohga, Hiroshi Kawame, Keiko Nakayama, Yoko Aoki, Naomichi MatsumotoTadashi Kaname, Yoichi Matsubara, Wataru Shoji, Shigeo Kure

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)927-933
Number of pages7
JournalAnnals of Neurology
Volume85
Issue number6
DOIs
Publication statusPublished - Jun 2019

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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  • Cite this

    Iwasawa, S., Yanagi, K., Kikuchi, A., Kobayashi, Y., Haginoya, K., Matsumoto, H., Kurosawa, K., Ochiai, M., Sakai, Y., Fujita, A., Miyake, N., Niihori, T., Shirota, M., Funayama, R., Nonoyama, S., Ohga, S., Kawame, H., Nakayama, K., Aoki, Y., ... Kure, S. (2019). Recurrent de novo MAPK8IP3 variants cause neurological phenotypes. Annals of Neurology, 85(6), 927-933. https://doi.org/10.1002/ana.25481