Mutations in α- and β-tubulin encoding genes: implications in brain malformations

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Tubulin gene family encodes α and β subunits forming microtubules, essential for neuronal development.
• These genes are crucial for neuronal migration and axonal guidance during Central Nervous System development.
• Mutations in tubulin genes can alter microtubule dynamics, affecting neuronal processes.

Purpose of the Study:

• To review the structural and functional features of tubulin genes.
• To revise major cerebral malformations associated with tubulin gene mutations.
• To suggest genotype-phenotype correlations for these conditions.

Main Methods:

• Literature review of studies on tubulin genes and associated brain malformations.
• Analysis of structural and functional characteristics of tubulin proteins.
• Correlation of genetic mutations with observed phenotypes.

Main Results:

• Tubulin gene mutations are linked to cortical malformations (lissencephaly, polymicrogyria, schizencephaly) due to altered neuronal migration.
• Mutations also cause midline commissural structure abnormalities and hind-brain dysmorphisms, reflecting axon guidance defects.
• Rare conditions like H-ABC leukoencephalopathy are associated with tubulin gene defects.

Conclusions:

• Tubulin gene mutations are a significant cause of diverse congenital brain malformations.
• Understanding genotype-phenotype correlations aids in diagnosing and managing these complex neurological disorders.
• Further research into tubulin gene function is critical for advancing neurodevelopmental disorder treatments.