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Polymicrogyria with dysmorphic basal ganglia? Think tubulin!
Author(s) -
Amrom D.,
Tanyalçin I.,
Verhelst H.,
Deconinck N.,
Brouhard G.J.,
Décarie J.C.,
Vanderhasselt T.,
Das S.,
Hamdan F.F.,
Lissens W.,
Michaud J.L.,
Jansen A.C.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12141
Subject(s) - polymicrogyria , corpus callosum , cerebellar vermis , biology , white matter , hypoplasia , mutation , sanger sequencing , agenesis of the corpus callosum , basal ganglia , brainstem , genetics , anatomy , pathology , cerebellum , neuroscience , medicine , central nervous system , magnetic resonance imaging , epilepsy , gene , radiology
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.