ALS due to a novel TBK1 mutation in Brazil

Abstract

TANK-binding kinase 1 (TBK1) gene mutations cause ALS and frontotemporal dementia (FTD). We report a novel TBK1 mutation in a Brazilian patient with ALS. Symptoms started at age 44 (lower-limb onset). Despite treatment with riluzole, his condition progressed over 5 years to aphemia, dysphagia, gastrostomy and tracheostomy. A diagnostic test panel for neurodegenerative disorders disclosed a novel likely pathogenic heterozygous intronic mutation in the TBK1 gene: c.1189 + 1G > T (Splice donor), intron 9. This mutation is expected to disrupt RNA splicing and lead to loss of protein function. Disruption of this splice site has been observed in patients with TBK1-related disorders. Separate and additional C9ORFF72 testing was negative. To our knowledge, this is the second patient with a TBK1 mutation (novel splice donor intronic mutation) reported in Brazil, and the first to include a full description of the clinical course. Further studies are necessary to establish the frequency of TBK1 mutations in Brazilian ALS patients (and worldwide) and to evaluate the possible different clinical phenotypes and the disease course.

Keywords:

• Amyotrophic lateral sclerosis
• TBK1 gene
• genetics
• epidemiology

Ethical approval

Informed consent has been obtained from the patient

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Acknowledgements

The authors would like to thank the company Invitae for providing free genetic testing (66 gene panel) for disease detection in this patient.