TUBA1A Mutation Associated With Eye Abnormalities in Addition to Brain Malformation

We describe the case of a boy with a TUBA1A mutation presenting with microphthalmia and congenital cataracts in addition to microcephaly and severe brain malformation.

A boy presented in early infancy with microphthalmia, congenital cataracts, and microcephaly. His neurological course included severe hypotonia and drug-resistant epilepsy. Magnetic resonance imaging of the brain revealed a complex malformation that included agenesis of the corpus callosum, severely hypoplastic cerebellar vermis, mildly hypoplastic and dysplastic cerebellar hemispheres, mildly hypoplastic brainstem, mild posterior simplified cerebral gyral pattern, dysplastic basal ganglia and thalami, hypoplastic optic nerves, and absent olfactory bulbs.

TUBA1A genetic testing was conducted and revealed a previously unreported heterozygous 808G>T missense mutation. Parental genetic testing was negative, indicating that the child's mutation was de novo.

The TUBA1A gene encodes tubulin alpha-1A, a protein with an important role in microtubule function and stability. Human mutations can result in a wide spectrum of brain malformations including lissencephaly, microlissencephaly, cerebellar hypoplasia, agenesis of the corpus callosum, pachygyria and polymicrogyria. Although TUBA1A is expressed in both developing brain and retinal tissue, there are no reported cases of TUBA1A mutations in association with major developmental ophthalmologic abnormalities.