Recurrent de novo MAPK8IP3 variants cause neurological phenotypes.
Ann Neurol
; 85(6): 927-933, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-30945334
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;85927-933.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Variación Genética
/
Proteínas Adaptadoras Transductoras de Señales
/
Proteínas del Tejido Nervioso
/
Enfermedades del Sistema Nervioso
Límite:
Adolescent
/
Adult
/
Animals
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Ann Neurol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón