Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature genetics, 2014-12, Vol.46 (12), p.1283-1292

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2014

Link zum Volltext

Beschreibungen/Notizen

• 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.