Recurrent de novo MAPK8IP3 variants cause neurological phenotypes.
Ann Neurol
; 85(6): 927-933, 2019 06.
Article
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Variação Genética
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas do Tecido Nervoso
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Doenças do Sistema Nervoso
Limite:
Adolescent
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Adult
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Animals
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão