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

Juliane Najm, 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

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1065-1067
Number of pages3
JournalNature Genetics
Volume40
Issue number9
DOIs
StatePublished - Sep 2008
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to the study participants and their parents. We thank I. Jantke, L. Schroedter and F. Trotier for skillful technical assistance, S. Fuchs and K. Ziegler for chromosome analysis, and A. Nowka for help with the in vitro splicing assay. We also thank T. Südhof (Howard Hughes Medical Institute) for providing Cask knock-in mice. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (KU 1240/3-2 to K.K.), and a grant from the US National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01-NS050375 to W.B.D.).

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