Polymicrogyria with dismorphic basal ganglia? Think tuberculin! (accepted)

Background: Dominant mutations in TUBB2B have been reported in patients with
polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B.
Methods: Twenty patients with polymicrogyria (5 unilateral) were tested for mutations in
TUBB2B by Sanger sequencing.
Results: 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 MRIs
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.
Conclusions: 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.

Jaar van publicatie:2013

Trefwoorden:polymicrogyria, Malformations of cortical development, TUBB2B, corpus callosum, Basal ganglia