Objective: To describe the first case of a rare variant of the TUBB4A gene in a Brazilian individual

Background: TUBB4A-related leukodystrophy presents with various clinical symptoms, such as neuropsychomotor development delay, followed by movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonos and oculogyric crises, progressive spastic tetraplegia, ataxia and, more rarely, seizures. The disease has a characteristic hypomyelination on MRI, which may be associated with basal ganglia and cerebellum atrophy^1. This condition is known as hypomyelinating leukodystrophy-6 (#612438), caused by a heterozygous mutation in the TUBB4A gene (*602662) in the chromosome 19p13. Due to its spectral characteristic, it can be used with several clinical presentations, including case of dystonia DYT-TUBB4A. We will describe a rare pathogenic variant in the TUBB4 gene (c.286G>A (p.Gly96Arg), point mutation, autosomal dominant, with no description of pathogenicity in the literature^2,3. This variant was described only in Asiatic population

Method: Case report of a single patient. Parts of this abstract had been presented at the Brazilian Congress of Neurology in 2022 and published in a digital abstract record of the event.

Results: We describe a 35-year-old female with a progressive lower limbs weakness, being restricted to the wheelchair for the past four years, associated with refractory epilepsy. Previously, the patient had a motor delay with neuropsychiatric symptoms, being diagnosed with schizophrenia at age of 13. Neurological examination showed a moderate cognitive impairment and spastic paraparesis, associated with dystonia in the lower limbs. MRI showed a diffuse cortical and cerebellar atrophy and white matter disease, suggestive of hypomyelinating leukodystrophy (Fig 1). After a last genetic testing, she received the diagnosis of hypomyelinating leukodystrophy-6 (#612438) by pathogenic variant NM_006087.4(TUBB4A): c.286G>A (p.Gly96Arg) in the TUBB4A gene.

Conclusion: Patients presenting neuropsychiatric symptoms associated with motor impairment, especially dystonia, must be investigated for leukodystrophy. It is important to constantly update genetic tests database to carry out molecular diagnosis, aiming mainly to confirm diagnostics and reproductive counselling.

References: 1. Nahhas N, Conant A, Hamilton E, et al. TUBB4A-Related Leukodystrophy. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; November 3, 2016
2. Krajka V, Vulinovic F, Genova M, et al. H-ABC- and dystonia-causing TUBB4A mutations show distinct pathogenic effects. Sci Adv. 2022;8(10):eabj9229. doi:10.1126/sciadv.abj9229
3.https://www.ncbi.nlm.nih.gov/clinvar/

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