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, Shoichi Ohga, Hiroshi Kawame, Keiko Nakayama, Yoko Aoki, Naomichi Matsumoto & 4 others Tadashi Kaname, Yoichi Matsubara, Wataru Shoji, Shigeo Kure

Research output: Contribution to journalArticle

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 1 2019

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Adaptor Protein Complex 1
Axons
Phenotype
Kinesin
Axonal Transport
JNK Mitogen-Activated Protein Kinases
Corpus Callosum
Zebrafish
Cerebral Palsy
Intellectual Disability
Atrophy
Embryonic Structures
Neurons
Proteins

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Iwasawa, S., Yanagi, K., Kikuchi, A., Kobayashi, Y., Haginoya, K., Matsumoto, H., ... 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

Recurrent de novo MAPK8IP3 variants cause neurological phenotypes. / Iwasawa, Shinya; Yanagi, Kumiko; Kikuchi, Atsuo; Kobayashi, Yasuko; Haginoya, Kazuhiro; Matsumoto, Hiroshi; Kurosawa, Kenji; Ochiai, Masayuki; Sakai, Yasunari; Fujita, Atsushi; Miyake, Noriko; Niihori, Tetsuya; Shirota, Matsuyuki; Funayama, Ryo; Nonoyama, Shigeaki; Ohga, Shoichi; Kawame, Hiroshi; Nakayama, Keiko; Aoki, Yoko; Matsumoto, Naomichi; Kaname, Tadashi; Matsubara, Yoichi; Shoji, Wataru; Kure, Shigeo.

In: Annals of Neurology, Vol. 85, No. 6, 01.06.2019, p. 927-933.

Research output: Contribution to journalArticle

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, Matsumoto, N, Kaname, T, Matsubara, Y, Shoji, W & Kure, S 2019, 'Recurrent de novo MAPK8IP3 variants cause neurological phenotypes', Annals of Neurology, vol. 85, no. 6, pp. 927-933. https://doi.org/10.1002/ana.25481
Iwasawa S, Yanagi K, Kikuchi A, Kobayashi Y, Haginoya K, Matsumoto H et al. Recurrent de novo MAPK8IP3 variants cause neurological phenotypes. Annals of Neurology. 2019 Jun 1;85(6):927-933. https://doi.org/10.1002/ana.25481
Iwasawa, Shinya ; Yanagi, Kumiko ; Kikuchi, Atsuo ; Kobayashi, Yasuko ; Haginoya, Kazuhiro ; Matsumoto, Hiroshi ; Kurosawa, Kenji ; Ochiai, Masayuki ; Sakai, Yasunari ; Fujita, Atsushi ; Miyake, Noriko ; Niihori, Tetsuya ; Shirota, Matsuyuki ; Funayama, Ryo ; Nonoyama, Shigeaki ; Ohga, Shoichi ; Kawame, Hiroshi ; Nakayama, Keiko ; Aoki, Yoko ; Matsumoto, Naomichi ; Kaname, Tadashi ; Matsubara, Yoichi ; Shoji, Wataru ; Kure, Shigeo. / Recurrent de novo MAPK8IP3 variants cause neurological phenotypes. In: Annals of Neurology. 2019 ; Vol. 85, No. 6. pp. 927-933.
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AU - Kikuchi, Atsuo

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AU - Matsumoto, Hiroshi

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AU - Kawame, Hiroshi

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AU - Aoki, Yoko

AU - Matsumoto, Naomichi

AU - Kaname, Tadashi

AU - Matsubara, Yoichi

AU - Shoji, Wataru

AU - Kure, Shigeo

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