Recurrent de novo MAPK8IP3 variants cause neurological phenotypes.

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 Phenotype Zebrafish

Journal

Annals of neurology

ISSN: 1531-8249

Titre abrégé: Ann Neurol

Pays: United States

ID NLM: 7707449

Informations de publication

Date de publication:
06 2019

Historique:

received: 17 12 2018

revised: 01 04 2019

accepted: 03 04 2019

pubmed: 5 4 2019

medline: 31 3 2020

entrez: 5 4 2019

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1002/ana.25481 PMID: 30945334

pubmed: 30945334

doi: 10.1002/ana.25481

doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0

MAPK8IP3 protein, human 0

Nerve Tissue Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng