Universität zu Köln

Yigit, Goekhan, Brown, Karen E., Kayserili, Hulya ORCID: 0000-0003-0376-499X, Pohl, Esther, Caliebe, Almuth ORCID: 0000-0003-2157-425X, Zahnleiter, Diana, Rosser, Elisabeth, Boegershausen, Nina, Uyguner, Zehra Oya, Altunoglu, Umut, Nuernberg, Gudrun, Nuernberg, Peter, Rauch, Anita ORCID: 0000-0003-2930-3163, Li, Yun, Thiel, Christian Thomas and Wollnik, Bernd (2015). Mutations in CDK5RAP2 cause Seckel syndrome. Mol. Genet. Genom. Med., 3 (5). S. 467 - 481. HOBOKEN: WILEY. ISSN 2324-9269

Full text not available from this repository.

Abstract

Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. Here, we describe the novel homozygous splice-site mutations c. 383+ 1G>C and c. 4005-9A>G in CDK5RAP2 in two consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal protein which is known to be essential for centrosomal cohesion and proper spindle formation and has been shown to be causally involved in autosomal recessive primary microcephaly. We establish CDK5RAP2 as a disease-causing gene for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosomal and mitotic proteins in the pathogenesis of the disease. Additionally, we present an intriguing case of possible digenic inheritance in Seckel syndrome: A severely affected child of nonconsanguineous German parents was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding points toward a potential additive genetic effect of mutations in CDK5RAP2 and CEP152.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Yigit, Goekhan UNSPECIFIED UNSPECIFIED UNSPECIFIED Brown, Karen E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kayserili, Hulya UNSPECIFIED orcid.org/0000-0003-0376-499X UNSPECIFIED Pohl, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Caliebe, Almuth UNSPECIFIED orcid.org/0000-0003-2157-425X UNSPECIFIED Zahnleiter, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosser, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Boegershausen, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Uyguner, Zehra Oya UNSPECIFIED UNSPECIFIED UNSPECIFIED Altunoglu, Umut UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauch, Anita UNSPECIFIED orcid.org/0000-0003-2930-3163 UNSPECIFIED Li, Yun UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiel, Christian Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wollnik, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-395755
DOI:	10.1002/mgg3.158
Journal or Publication Title:	Mol. Genet. Genom. Med.
Volume:	3
Number:	5
Page Range:	S. 467 - 481
Date:	2015
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2324-9269
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CEPHALIC PRIMORDIAL DWARFISM; II MOPD-II; CELLULAR-FEATURES; PROTEIN; CENTROSOME; BRAIN; GENE; ATTACHMENT; REVEALS; PROGRAM Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39575