2. Academic Validation
  3. Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria

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

  • Nat Genet. 2009 Jun;41(6):746-52. doi: 10.1038/ng.380.
Xavier Hubert Jaglin 1,  Karine Poirier,  Yoann Saillour,  Emmanuelle Buhler,  Guoling Tian,  Nadia Bahi-Buisson,  Catherine Fallet-Bianco,  Françoise Phan-Dinh-Tuy,  Xiang Peng Kong,  Pascale Bomont,  Laëtitia Castelnau-Ptakhine,  Sylvie Odent,  Philippe Loget,  Manoelle Kossorotoff,  Irina Snoeck,  Ghislaine Plessis,  Philippe Parent,  Cherif Beldjord,  Carlos Cardoso,  Alfonso Represa,  Jonathan Flint,  David Anthony Keays,  Nicholas Justin Cowan,  Jamel Chelly
Affiliations

Affiliation

  • 1 Institut Cochin, Université Paris Descartes CNRS (UMR 8104), Paris, France.
PMID: 19465910 DOI: 10.1038/ng.380
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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