title: Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly.
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).
authors: Catherine
authors: C
authors: Fallet-Bianco
authors: Annie
authors: A
authors: Laquerrière
authors: Karine
authors: K
authors: Poirier
authors: Ferechte
authors: F
authors: Razavi
authors: Fabien
authors: F
authors: Guimiot
authors: Patricia
authors: P
authors: Dias
authors: Laurence
authors: L
authors: Loeuillet
authors: Karine
authors: K
authors: Lascelles
authors: Cherif
authors: C
authors: Beldjord
authors: Nathalie
authors: N
authors: Carion
authors: Aurélie
authors: A
authors: Toussaint
authors: Nicole
authors: N
authors: Revencu
authors: Marie-Claude
authors: MC
authors: Addor
authors: Benoit
authors: B
authors: Lhermitte
authors: Marie
authors: M
authors: Gonzales
authors: Jelena
authors: J
authors: Martinovich
authors: Bettina
authors: B
authors: Bessieres
authors: Maryse
authors: M
authors: Marcy-Bonnière
authors: Frédérique
authors: F
authors: Jossic
authors: Pascale
authors: P
authors: Marcorelles
authors: Philippe
authors: P
authors: Loget
authors: Jamel
authors: J
authors: Chelly
authors: Institut Imagine, Université Paris Descartes - Sorbonne Paris Cités, Paris, France. nadia.bahi-buisson@nck.aphp.fr.
authors: Nadia
authors: N
authors: Bahi-Buisson
mesh_terms: D001344:Autopsy; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D005333:Fetus; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D065703:Malformations of Cortical Development, Group I / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D014404:Tubulin / Q000235:genetics*
chemical_list: D014404:Tubulin