Stephen, Louise A., Tawamie, Hasan, Davis, Gemma M., Tebbe, Lars, Nuernberg, Peter, Nuernberg, Gudrun, Thiele, Holger, Thoenes, Michaela, Boltshauser, Eugen, Uebe, Steffen, Rompel, Oliver, Reis, Andre ORCID: 0000-0002-6301-6363, Ekici, Arif B., McTeir, Lynn, Fraser, Amy M., Hall, Emma A., Mill, Pleasantine ORCID: 0000-0001-5218-134X, Daudet, Nicolas ORCID: 0000-0002-4039-4716, Cross, Courtney ORCID: 0000-0001-5345-9614, Wolfrum, Uwe, Abou Jamra, Rami, Davey, Megan G. and Bolz, Hanno J. (2015). TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23). eLife, 4. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

Joubert syndrome (JBTS) is a severe recessive neurodevelopmental ciliopathy which can affect several organ systems. Mutations in known JBTS genes account for approximately half of the cases. By homozygosity mapping and whole-exome sequencing, we identified a novel locus, JBTS23, with a homozygous splice site mutation in KIAA0586 (alias TALPID3), a known lethal ciliopathy locus in model organisms. Truncating KIAA0586 mutations were identified in two additional patients with JBTS. One mutation, c.428delG (p.Arg143Lysfs*4), is unexpectedly common in the general population and may be a major contributor to JBTS. We demonstrate KIAA0586 protein localization at the basal body in human and mouse photoreceptors, as is common for JBTS proteins, and also in pericentriolar locations. We show that loss of TALPID3 (KIAA0586) function in animal models causes abnormal tissue polarity, centrosome length and orientation, and centriolar satellites. We propose that JBTS and other ciliopathies may in part result from cell polarity defects.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Stephen, Louise A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tawamie, HasanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, Gemma M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tebbe, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, GudrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thoenes, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boltshauser, EugenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uebe, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rompel, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reis, AndreUNSPECIFIEDorcid.org/0000-0002-6301-6363UNSPECIFIED
Ekici, Arif B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McTeir, LynnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fraser, Amy M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, Emma A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mill, PleasantineUNSPECIFIEDorcid.org/0000-0001-5218-134XUNSPECIFIED
Daudet, NicolasUNSPECIFIEDorcid.org/0000-0002-4039-4716UNSPECIFIED
Cross, CourtneyUNSPECIFIEDorcid.org/0000-0001-5345-9614UNSPECIFIED
Wolfrum, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abou Jamra, RamiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davey, Megan G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolz, Hanno J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-392852
DOI: 10.7554/eLife.08077
Journal or Publication Title: eLife
Volume: 4
Date: 2015
Publisher: ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RECESSIVE INTELLECTUAL DISABILITY; PROTEIN; CILIA; GENE; MUTATIONS; RAB8; CILIOGENESIS; REVEALS; LOCALIZATION; ENCODESMultiple languages
BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39285

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