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.
Citation
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. 85(6):927-933.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping