PUBLICATION
Novel CASK mutations in cases with syndromic microcephaly
- Authors
- Cristofoli, F., Devriendt, K., Davis, E.E., Van Esch, H., Vermeesch, J.R.
- ID
- ZDB-PUB-180426-12
- Date
- 2018
- Source
- Human Mutation 39(7): 993-1001 (Journal)
- Registered Authors
- Davis, Erica
- Keywords
- CASK, cerebellar defects, loss-of-function, microcephaly, zebrafish
- MeSH Terms
-
- Animals
- Cerebellum/physiopathology
- Exome Sequencing
- Female
- Genes, X-Linked/genetics
- Genetic Predisposition to Disease*
- Guanylate Kinases/genetics*
- Humans
- Intellectual Disability/genetics*
- Intellectual Disability/physiopathology
- Loss of Function Mutation/genetics
- Male
- Microcephaly/genetics*
- Microcephaly/physiopathology
- Mutation
- Phenotype
- Zebrafish/genetics
- PubMed
- 29691940 Full text @ Hum. Mutat.
Citation
Cristofoli, F., Devriendt, K., Davis, E.E., Van Esch, H., Vermeesch, J.R. (2018) Novel CASK mutations in cases with syndromic microcephaly. Human Mutation. 39(7):993-1001.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping