Novel CASK mutations in cases with syndromic microcephaly.


Journal Article

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.

Full Text

Cited Authors

  • Cristofoli, F; Devriendt, K; Davis, EE; Van Esch, H; Vermeesch, JR

Published Date

  • July 2018

Published In

Volume / Issue

  • 39 / 7

Start / End Page

  • 993 - 1001

PubMed ID

  • 29691940

Pubmed Central ID

  • 29691940

Electronic International Standard Serial Number (EISSN)

  • 1098-1004

International Standard Serial Number (ISSN)

  • 1059-7794

Digital Object Identifier (DOI)

  • 10.1002/humu.23536


  • eng