Polymicrogyria with dysmorphic basal ganglia? Think tubulin!

Area of Science:

• Genetics
• Neurology
• Developmental Biology

Background:

• Mutations in the TUBB2B gene are associated with polymicrogyria.
• Further characterization of the phenotype linked to TUBB2B mutations is needed.

Purpose of the Study:

• To investigate the phenotype associated with TUBB2B mutations in patients with polymicrogyria.
• To identify novel mutations in TUBB2B.

Main Methods:

• Sanger sequencing of the TUBB2B gene in 20 patients with polymicrogyria.
• Analysis of brain magnetic resonance imaging (MRI) findings.

Main Results:

• Identified two novel de novo mutations in TUBB2B (c.743C>T and c.1139G>T) in three families.
• Observed polymicrogyria, particularly in perisylvian regions, along with dysmorphic basal ganglia, thin corpus callosum, enlarged ventricles, white matter thinning, and hypoplasia of the pons and cerebellar vermis.
• This specific combination of features was not present in patients without TUBB2B mutations.

Conclusions:

• The association of polymicrogyria with specific brain abnormalities is strongly linked to TUBB2B mutations.
• These findings provide insights into the functional impact of TUBB2B mutations on brain development.