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DOI 10.1038/ng.3122

Медицинская библиотека · Nature genetics · 2014

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

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

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Аннотация

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.

Для цитирования: 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. Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.. Nature genetics. 2014. DOI: 10.1038/ng.3122.

Предметные рубрики MeSH

AdolescentAdultAnimalsCentriolesChildChild, PreschoolFamily HealthFemaleFibroblastsGenotypeGrowth DisordersHeLa CellsHumansIn Situ Hybridization, FluorescenceInfantMaleMicrocephalyMicrosatellite RepeatsMicrotubule-Associated ProteinsMitosisMutationPakistanPedigreePhenotypeProtein Serine-Threonine KinasesRetinal DegenerationYoung AdultZebrafish
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