title: Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria.
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.
authors.affiliation: Institut Cochin, Université Paris Descartes CNRS (UMR 8104), Paris, France.
authors.forename: Xavier Hubert
authors.initials: XH
authors.lastname: Jaglin
authors.forename: Karine
authors.initials: K
authors.lastname: Poirier
authors.forename: Yoann
authors.initials: Y
authors.lastname: Saillour
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Buhler
authors.forename: Guoling
authors.initials: G
authors.lastname: Tian
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.forename: Catherine
authors.initials: C
authors.lastname: Fallet-Bianco
authors.forename: Françoise
authors.initials: F
authors.lastname: Phan-Dinh-Tuy
authors.forename: Xiang Peng
authors.initials: XP
authors.lastname: Kong
authors.forename: Pascale
authors.initials: P
authors.lastname: Bomont
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Castelnau-Ptakhine
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Philippe
authors.initials: P
authors.lastname: Loget
authors.forename: Manoelle
authors.initials: M
authors.lastname: Kossorotoff
authors.forename: Irina
authors.initials: I
authors.lastname: Snoeck
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Plessis
authors.forename: Philippe
authors.initials: P
authors.lastname: Parent
authors.forename: Cherif
authors.initials: C
authors.lastname: Beldjord
authors.forename: Carlos
authors.initials: C
authors.lastname: Cardoso
authors.forename: Alfonso
authors.initials: A
authors.lastname: Represa
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.forename: David Anthony
authors.initials: DA
authors.lastname: Keays
authors.forename: Nicholas Justin
authors.initials: NJ
authors.lastname: Cowan
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D005315:Fetal Diseases / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D054082:Lissencephaly / Q000235:genetics; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010841:Pia Mater / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D014404:Tubulin / Q000235:genetics*
chemical_list: C576987:TUBB2B protein, human; D014404:Tubulin