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Novel CASK mutations in cases with syndromic microcephaly
- Source :
- Human Mutation. 39:993-1001
- Publication Year :
- 2018
- Publisher :
- Hindawi Limited, 2018.
-
Abstract
- Mutations in CASK cause a wide spectrum of phenotypes in humans ranging from mild X-linked intellectual disability to a severe microcephaly (MC) and pontocerebellar hypoplasia syndrome. Nevertheless, predicting pathogenicity and phenotypic consequences of novel CASK mutations through the exclusive consideration of genetic information and population-based data remains a challenge. Using whole exome sequencing, we identified four novel CASK mutations in individuals with syndromic MC. To understand the functional consequences of the different point mutations on the development of MC and cerebellar defects we established a transient loss of function zebrafish model, and demonstrate recapitulation of relevant neuroanatomical phenotypes. Furthermore, we utilized in vivo complementation studies to demonstrate that the three point mutations confer a loss of function effect. This work endorses zebrafish as a tractable model to rapidly assess the effect of novel CASK variants on brain development. This article is protected by copyright. All rights reserved. ispartof: Human Mutation vol:39 issue:7 pages:993-1001 ispartof: location:United States status: published
- Subjects :
- Male
0301 basic medicine
Microcephaly
Population
Pontocerebellar hypoplasia
Article
03 medical and health sciences
Genes, X-Linked
Loss of Function Mutation
Cerebellum
Intellectual Disability
Exome Sequencing
Genetics
medicine
Animals
Humans
Genetic Predisposition to Disease
CASK
education
Zebrafish
Genetics (clinical)
Exome sequencing
Loss function
education.field_of_study
biology
Point mutation
medicine.disease
biology.organism_classification
Phenotype
030104 developmental biology
Mutation
Female
Guanylate Kinases
Subjects
Details
- ISSN :
- 10597794
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Human Mutation
- Accession number :
- edsair.doi.dedup.....073d5e8c953e412b7e610905eaa9bb42