title: Polymicrogyria with dysmorphic basal ganglia? Think tubulin!
abstract: Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.
authors.affiliation: Centre of Excellence in Neurosciences of Université de Montréal and Sainte-Justine Hospital Research Center; Neurogenetics Unit, Montreal Neurological Hospital, McGill University, Montreal, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Amrom
authors.forename: I
authors.initials: I
authors.lastname: Tanyalçin
authors.forename: H
authors.initials: H
authors.lastname: Verhelst
authors.forename: N
authors.initials: N
authors.lastname: Deconinck
authors.forename: G J
authors.initials: GJ
authors.lastname: Brouhard
authors.forename: J-C
authors.initials: JC
authors.lastname: Décarie
authors.forename: T
authors.initials: T
authors.lastname: Vanderhasselt
authors.forename: S
authors.initials: S
authors.lastname: Das
authors.forename: F F
authors.initials: FF
authors.lastname: Hamdan
authors.forename: W
authors.initials: W
authors.lastname: Lissens
authors.forename: J L
authors.initials: JL
authors.lastname: Michaud
authors.forename: A C
authors.initials: AC
authors.lastname: Jansen
mesh_terms: D001479:Basal Ganglia / Q000473:pathology*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010641:Phenotype; D065706:Polymicrogyria / Q000235:genetics* / Q000473:pathology*; D014404:Tubulin / Q000235:genetics*
chemical_list: C576987:TUBB2B protein, human; D014404:Tubulin; D004398:Dyneins
keywords: TUBB2B; basal ganglia; corpus callosum; malformations of cortical development; polymicrogyria