Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly.

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Serval ID
serval:BIB_E0BDFE630A77
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly.
Journal
Acta Neuropathologica Communications
Author(s)
Fallet-Bianco C., Laquerrière A., Poirier K., Razavi F., Guimiot F., Dias P., Addor M.C., Loeuillet L., Lascelles K., Beldjord C., Carion N., Toussaint A., Revencu N., Lhermitte B., Gonzales M., Martinovich J., Bessieres B., Marcy-Bonnière M., Jossic F., Marcorelles P., Loget P., Chelly J., Bahi-Buisson N.
ISSN
2051-5960 (Electronic)
ISSN-L
2051-5960
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
2
Pages
69
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
Complex cortical malformations associated with mutations in tubulin genes are commonly referred to as "Tubulinopathies". To further characterize the mutation frequency and phenotypes associated with tubulin mutations, we studied a cohort of 60 foetal cases. Twenty-six tubulin mutations were identified, of which TUBA1A mutations were the most prevalent (19 cases), followed by TUBB2B (6 cases) and TUBB3 (one case). Three subtypes clearly emerged. The most frequent (n = 13) was microlissencephaly with corpus callosum agenesis, severely hypoplastic brainstem and cerebellum. The cortical plate was either absent (6/13), with a 2-3 layered pattern (5/13) or less frequently thickened (2/13), often associated with neuroglial overmigration (4/13). All cases had voluminous germinal zones and ganglionic eminences. The second subtype was lissencephaly (n = 7), either classical (4/7) or associated with cerebellar hypoplasia (3/7) with corpus callosum agenesis (6/7). All foetuses with lissencephaly and cerebellar hypoplasia carried distinct TUBA1A mutations, while those with classical lissencephaly harbored recurrent mutations in TUBA1A (3 cases) or TUBB2B (1 case). The third group was polymicrogyria-like cortical dysplasia (n = 6), consisting of asymmetric multifocal or generalized polymicrogyria with inconstant corpus callosum agenesis (4/6) and hypoplastic brainstem and cerebellum (3/6). Polymicrogyria was either unlayered or 4-layered with neuronal heterotopias (5/6) and occasional focal neuroglial overmigration (2/6). Three had TUBA1A mutations and 3 TUBB2B mutations. Foetal TUBA1A tubulinopathies most often consist in microlissencephaly or classical lissencephaly with corpus callosum agenesis, but polymicrogyria may also occur. Conversely, TUBB2B mutations are responsible for either polymicrogyria (4/6) or microlissencephaly (2/6).
Keywords
Autopsy, Brain/abnormalities, Brain/metabolism, DNA Mutational Analysis, Female, Fetus, Humans, Magnetic Resonance Imaging, Male, Malformations of Cortical Development, Group I/classification, Malformations of Cortical Development, Group I/diagnosis, Mutation/genetics, Tubulin/genetics
Pubmed
Open Access
Yes
Create date
27/01/2015 10:15
Last modification date
20/08/2019 16:04
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