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.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Jaglin XH,Poirier K,Saillour Y,Buhler E,Tian G,Bahi-Buisson N,Fallet-Bianco C,Phan-Dinh-Tuy F,Kong XP,Bomont P,Castelnau-Ptakhine L,Odent S,Loget P,Kossorotoff M,Snoeck I,Plessis G,Parent P,Beldjord C,Cardoso C,Reprdoi
10.1038/ng.380subject
Has Abstractpub_date
2009-06-01 00:00:00pages
746-52issue
6eissn
1061-4036issn
1546-1718pii
ng.380journal_volume
41pub_type
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