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.
journal_name
Hum Mutatjournal_title
Human mutationauthors
Cristofoli F,Devriendt K,Davis EE,Van Esch H,Vermeesch JRdoi
10.1002/humu.23536subject
Has Abstractpub_date
2018-07-01 00:00:00pages
993-1001issue
7eissn
1059-7794issn
1098-1004journal_volume
39pub_type
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