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ZFIN ID: ZDB-PUB-190405-17
Recurrent de novo MAPK8IP3 variants cause neurological phenotypes
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.
Date: 2019
Source: Annals of neurology   85(6): 927-933 (Other)
Registered Authors: Shoji, Wataru
Keywords: JIP3, MAPK8IP3
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/genetics*
  • Adolescent
  • Adult
  • Animals
  • Child, Preschool
  • Female
  • Genetic Variation/genetics*
  • Humans
  • Male
  • Nerve Tissue Proteins/genetics*
  • Nervous System Diseases/diagnostic imaging*
  • Nervous System Diseases/genetics*
  • Phenotype*
  • Zebrafish
PubMed: 30945334 Full text @ Ann. Neurol.
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 five 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. This article is protected by copyright. All rights reserved.