Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum

  • Nat Genet. 2008 Sep;40(9):1065-7. doi: 10.1038/ng.194.
Juliane Najm  1 ,  Denise Horn ,  Isabella Wimplinger ,  Jeffrey A Golden ,  Victor V Chizhikov ,  Jyotsna Sudi ,  Susan L Christian ,  Reinhard Ullmann ,  Alma Kuechler ,  Carola A Haas ,  Armin Flubacher ,  Lawrence R Charnas ,  Gökhan Uyanik ,  Ulrich Frank ,  Eva Klopocki ,  William B Dobyns ,  Kerstin Kutsche
Affiliations
  • 1. Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
PMID: 19165920 DOI: 10.1038/ng.194
Abstract

CASK is a multi-domain scaffolding protein that interacts with the transcription factor TBR1 and regulates expression of genes involved in cortical development such as RELN. Here we describe a previously unreported X-linked brain malformation syndrome caused by mutations of CASK. All five affected individuals with CASK mutations had congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia, and severe mental retardation.