Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 5, 1165-1170, 16 April 2008
doi:10.1016/j.ajhg.2008.03.001
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Truncation of the Down Syndrome Candidate Gene DYRK1A in Two Unrelated Patients with Microcephaly
Rikke S. Møller1, 2, Sabine Kübart3, Maria Hoeltzenbein3, Babett Heye4, Ida Vogel5, Christian P. Hansen2, Corinna Menzel3, Reinhard Ullmann3, Niels Tommerup1, Hans-Hilger Ropers3, Zeynep Tümer1, 
, 
and Vera M. Kalscheuer3
1 Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
2 Danish Epilepsy Centre, Dianalund, Kolonivej 1, 4293 Dianalund, Denmark
3 Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany
4 Institut für Soziale Pädiatrie und Jugendmedizin der Universität München, Abteilung Genetik, Kinderzentrum München, 81377 München, Germany
5 Department of Clinical Genetics, Aarhus University Hospital, The Bartholin Building, DK-8000 Aarhus C, Denmark
Corresponding authorAbstract
We have identified and characterized two unrelated patients with prenatal onset of microcephaly, intrauterine growth retardation, feeding problems, developmental delay, and febrile seizures/epilepsy who both carry a de novo balanced translocation that truncates the DYRK1A gene at chromosome 21q22.2. DYRK1A belongs to the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family, which is highly conserved throughout evolution. Given its localization in both the Down syndrome critical region and in the minimal region for partial monosomy 21, the gene has been studied intensively in animals and in humans, and DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with these syndromes. In the present study, we show that truncating mutations of DYRK1A result in a clinical phenotype including microcephaly.
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