Martin, Carol-Anne ORCID: 0000-0001-5914-2757, Ahmad, Ilyas, Klingseisen, Anna, Hussain, Muhammad Sajid ORCID: 0000-0002-1353-8809, Bicknell, Louise S., Leitch, Andrea, Nuernberg, Gudrun, Toliat, Mohammad Reza, Murray, Jennie E., Hunt, David, Khan, Fawad, Ali, Zafar ORCID: 0000-0002-2389-3337, Tinschert, Sigrid, Ding, James ORCID: 0000-0001-7273-9646, Keith, Charlotte, Harley, Margaret E., Heyn, Patricia, Mueller, Rolf, Hoffmann, Ingrid, Cormier-Daire, Valerie, Dollfus, Helene, Dupuis, Lucie, Bashamboo, Anu, McElreavey, Kenneth, Kariminejad, Ariana ORCID: 0000-0002-8467-4728, Mendoza-Londono, Roberto, Moore, Anthony T., Saggar, Anand, Schlechter, Catie, Weleber, Richard, Thiele, Holger, Altmueller, Janine, Hoehne, Wolfgang, Hurles, Matthew E., Noegel, Angelika Anna, Baig, Shahid Mahmood, Nuernberg, Peter and Jackson, Andrew P. (2014). Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nature Genet., 46 (12). S. 1283 - 1293. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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Abstract

Centrioles are essential for ciliogenesis. However, mutations in centriole biogenesis genes have been reported in primary microcephaly and Seckel syndrome, disorders without the hallmark clinical features of ciliopathies. Here we identify mutations in the genes encoding PLK4 kinase, a master regulator of centriole duplication, and its substrate TUBGCP6 in individuals with microcephalic primordial dwarfism and additional congenital anomalies, including retinopathy, thereby extending the human phenotypic spectrum associated with centriole dysfunction. Furthermore, we establish that different levels of impaired PLK4 activity result in growth and cilia phenotypes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Martin, Carol-AnneUNSPECIFIEDorcid.org/0000-0001-5914-2757UNSPECIFIED
Ahmad, IlyasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klingseisen, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hussain, Muhammad SajidUNSPECIFIEDorcid.org/0000-0002-1353-8809UNSPECIFIED
Bicknell, Louise S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leitch, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, GudrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toliat, Mohammad RezaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murray, Jennie E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunt, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, FawadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ali, ZafarUNSPECIFIEDorcid.org/0000-0002-2389-3337UNSPECIFIED
Tinschert, SigridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ding, JamesUNSPECIFIEDorcid.org/0000-0001-7273-9646UNSPECIFIED
Keith, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harley, Margaret E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heyn, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, IngridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cormier-Daire, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dollfus, HeleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dupuis, LucieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bashamboo, AnuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McElreavey, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kariminejad, ArianaUNSPECIFIEDorcid.org/0000-0002-8467-4728UNSPECIFIED
Mendoza-Londono, RobertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, Anthony T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saggar, AnandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlechter, CatieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weleber, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoehne, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hurles, Matthew E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noegel, Angelika AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baig, Shahid MahmoodUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jackson, Andrew P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-422724
DOI: 10.1038/ng.3122
Journal or Publication Title: Nature Genet.
Volume: 46
Number: 12
Page Range: S. 1283 - 1293
Date: 2014
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POLO-LIKE KINASE; CHROMOSOMAL INSTABILITY; MOUSE EMBRYO; CENTROSOMAL PROTEIN; HUMAN-CELLS; BRAIN SIZE; DUPLICATION; DISEASE; CEP152; CILIAMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42272

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