Brief Communication abstract


Nature Genetics 40, 1065 - 1067 (2008)
Published online: 10 August 2008 | Corrected online: 29 October 2008 | doi:10.1038/ng.194



There is a Corrigendum (November 2008) associated with this Brief Communication.

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

Juliane Najm1,13, Denise Horn2,13, Isabella Wimplinger1, Jeffrey A Golden3, Victor V Chizhikov4, Jyotsna Sudi4, Susan L Christian4, Reinhard Ullmann5, Alma Kuechler6, Carola A Haas7, Armin Flubacher7, Lawrence R Charnas8, Gökhan Uyanik9, Ulrich Frank10, Eva Klopocki2, William B Dobyns4,11,12 & Kerstin Kutsche1

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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.

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  1. Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
  2. Institut für Medizinische Genetik, Charité Universitätsmedizin, 13353 Berlin, Germany.
  3. Department of Pathology, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
  4. Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
  5. Max-Planck-Institut für Molekulare Genetik, 14195 Berlin, Germany.
  6. Institut für Humangenetik, Universitätsklinikum Essen, 45122 Essen, Germany.
  7. Experimental Epilepsy Research Group, Neurocenter, University of Freiburg, 79106 Freiburg, Germany.
  8. Division of Clinical Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
  9. Department of Neurology, University of Regensburg, 93053 Regensburg, Germany.
  10. Sozialpädiatrisches Zentrum, Städtisches Klinikum Braunschweig, 38118 Braunschweig, Germany.
  11. Departments of Neurology, University of Chicago, Chicago, Illinois 60637, USA.
  12. Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA.
  13. These authors contributed equally to this work.

Correspondence to: Kerstin Kutsche1 e-mail: kkutsche@uke.de

* NOTE: In the version of this article initially published, there was an error in the text on page 1066. The protein interacting with CASK is the CASK interacting nucleosome assembly protein (CINAP/TSPYL2) and not the TATA-binding protein associated factor TAF9. This error has been corrected in the HTML and PDF versions of the article.


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