PUBLICATION

Recurrent de novo MAPK8IP3 variants cause neurological phenotypes

Authors
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.
ID
ZDB-PUB-190405-17
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.
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping