Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy

Carol Anne Martin, Ilyas Ahmad, Anna Klingseisen, Muhammad Sajid Hussain, Louise S. Bicknell, Andrea Leitch, Gudrun Nürnberg, Mohammad Reza Toliat, Jennie E. Murray, David Hunt, Fawad Khan, Zafar Ali, Sigrid Tinschert, James Ding, Charlotte Keith, Margaret E. Harley, Patricia Heyn, Rolf Müller, Ingrid Hoffmann, Valérie Cormier DaireHélène Dollfus, Lucie Dupuis, Anu Bashamboo, Kenneth McElreavey, Ariana Kariminejad, Roberto Mendoza-Londono, Anthony T. Moore, Anand Saggar, Catie Schlechter, Richard Weleber, Holger Thiele, Janine Altmüller, Wolfgang Höhne, Matthew E. Hurles, Angelika Anna Noegel, Shahid Mahmood Baig, Peter Nürnberg, Andrew P. Jackson

Research output: Contribution to journalArticlepeer-review

137 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1283-1292
Number of pages10
JournalNature Genetics
Issue number12
Publication statusPublished - 11 Dec 2014
Externally publishedYes


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