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Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria.

Xavier Hubert Jaglin 1 Karine Poirier 1 Yoann Saillour 1 Emmanuelle Buhler 2 Guoling Tian 3 Nadia Bahi-Buisson 1, 4 Catherine Fallet-Bianco 5 Françoise Phan-Dinh-Tuy 1 Xiang Peng Kong 3 Pascale Bomont 2 Laëtitia Castelnau-Ptakhine 1 Sylvie Odent 6 Philippe Loget 7 Manoelle Kossorotoff 4 Irina Snoeck 8 Ghislaine Plessis 9 Philippe Parent 10 Cherif Beldjord 11 Carlos Cardoso 2 Alfonso Represa 2 Jonathan Flint 12 David Anthony Keays 13 Nicholas Justin Cowan 3, * Jamel Chelly 1, *
* Corresponding author
1 UMR_S567 / UMR 8104 - Institut Cochin
2 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
3 Department of Biochemistry
4 Service de neurologie pédiatrique [CHU Necker]
5 Service d'Anatomie Pathologique
6 Service de Génétique Clinique
7 Service d'anatomie et cytologie pathologiques [Rennes]
8 Locatie Juliana Kinderziekenhuis Polikliniek
9 Service de Génétique [CHU Caen]
10 Unité d'hémato-oncologie
11 Laboratoire de biochimie et génétique moléculaire
12 The Wellcome Trust Centre for Human Genetics [Oxford]
13 Institute of Molecular Pathology
Abstract : Polymicrogyria is a relatively common but poorly understood defect of cortical development characterized by numerous small gyri and a thick disorganized cortical plate lacking normal lamination. Here we report de novo mutations in a beta-tubulin gene, TUBB2B, in four individuals and a 27-gestational-week fetus with bilateral asymmetrical polymicrogyria. Neuropathological examination of the fetus revealed an absence of cortical lamination associated with the presence of ectopic neuronal cells in the white matter and in the leptomeningeal spaces due to breaches in the pial basement membrane. In utero RNAi-based inactivation demonstrates that TUBB2B is required for neuronal migration. We also show that two disease-associated mutations lead to impaired formation of tubulin heterodimers. These observations, together with previous data, show that disruption of microtubule-based processes underlies a large spectrum of neuronal migration disorders that includes not only lissencephaly and pachygyria, but also polymicrogyria malformations.
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CNRS | UNIV-RENNES1 | UNIV-PARIS5 | UNIV-AMU | USPC | UNIV-RENNES | COMUE-NORMANDIE | UNICAEN | UP-SANTE

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Xavier Hubert Jaglin, Karine Poirier, Yoann Saillour, Emmanuelle Buhler, Guoling Tian, et al.. Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria.. Nature Genetics, Nature Publishing Group, 2009, 41 (6), pp.746-752. ⟨10.1038/ng.380⟩. ⟨inserm-00404834⟩

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