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

doi:10.1038/ng.194

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 journal › Article › peer-review

240 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 language	English (US)
Pages (from-to)	1065-1067
Number of pages	3
Journal	Nature Genetics
Volume	40
Issue number	9
DOIs	https://doi.org/10.1038/ng.194
State	Published - Sep 2008
Externally published	Yes

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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Najm, J., Horn, D., Wimplinger, I., Golden, J. A., Chizhikov, V. V., Sudi, J., Christian, S. L., Ullmann, R., Kuechler, A., Haas, C. A., Flubacher, A., Charnas, L. R., Uyanik, G., Frank, U., Klopocki, E., Dobyns, W. B., & Kutsche, K. (2008). Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nature Genetics, 40(9), 1065-1067. https://doi.org/10.1038/ng.194

Najm, J, Horn, D, Wimplinger, I, Golden, JA, Chizhikov, VV, Sudi, J, Christian, SL, Ullmann, R, Kuechler, A, Haas, CA, Flubacher, A, Charnas, LR, Uyanik, G, Frank, U, Klopocki, E, Dobyns, WB & Kutsche, K 2008, 'Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum', Nature Genetics, vol. 40, no. 9, pp. 1065-1067. https://doi.org/10.1038/ng.194

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

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.",

author = "Juliane Najm and Denise Horn and Isabella Wimplinger and Golden, \{Jeffrey A.\} and Chizhikov, \{Victor V.\} and Jyotsna Sudi and Christian, \{Susan L.\} and Reinhard Ullmann and Alma Kuechler and Haas, \{Carola A.\} and Armin Flubacher and Charnas, \{Lawrence R.\} and G{\"o}khan Uyanik and Ulrich Frank and Eva Klopocki and Dobyns, \{William B.\} and Kerstin Kutsche",

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. S{\"u}dhof (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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AU - Horn, Denise

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AU - Golden, Jeffrey A.

AU - Chizhikov, Victor V.

AU - Sudi, Jyotsna

AU - Christian, Susan L.

AU - Ullmann, Reinhard

AU - Kuechler, Alma

AU - Haas, Carola A.

AU - Flubacher, Armin

AU - Charnas, Lawrence R.

AU - Uyanik, Gökhan

AU - Frank, Ulrich

AU - Klopocki, Eva

AU - Dobyns, William B.

AU - Kutsche, Kerstin

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

Abstract

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