[P1-192] A mild case of tubulinopathy with a novel missense mutation of the TUBA1A gene
【Background】 Tubulinopathies show a wide spectrum of brain malformations caused by dysfunction of tubulin-related genes. The TUBA1A gene encodes alfa-tubulin, dysfunction of which most frequently causes tubulinopathy characterized by diffuse agyria or perisylvian pachygyria with microcephaly, agenesis of the corpus callosum, and cerebellar hypoplasia. Here we report a mild case of tubulinopathy with a TUBA1A mutation.【Case presentation】The patient was 9 months old at her first visit. She showed gross motor delay at 4 months, and developed convulsion at 7 months of age. Her brain MRI showed porencephaly, occipital polymicrogyria, hypoplasia of the corpus callosum, volume loss of the white matter, dysgenesis of the anterior limb of the internal capsule, non-separated basal ganglia, cerebellar hypoplasia, and dysplastic brain stem. Whole exome sequencing identified a novel de novo heterozygous missense mutation in the TUBA1A gene, c.381C>A (p.Asp127Glu).【Discussion】Microtubules composed of tubulins regulate neuronal migration and lamination as well as axon guidance. Tubulinopathies affect normal development of the corpus callosum and white matter as well as neuronal migration, as seen in the present patient. Patients with TUBA1A mutations generally show more severe cortical abnormality than our patient. Genotype-phenotype correlation remains unclear; however, this study expanded the phenotypic range of tubulinopathies.【Conclusion】Tubulinpathy caused by a TUBA1A mutation demonstrated variable phenotypes, such as porencephaly, focal polymicrogyria, and hypoplastic, but lacked aplastic corpus callosum.