Clinicopathologic correlations in a family with a TBK1 mutation presenting as primary progressive aphasia and primary lateral sclerosis

Veronica Hirsch-Reinshagen, Omar A. Alfaify, Ging Yuek R. Hsiung, Cyril Pottier, Matt Baker, Ralph B. Perkerson, Rosa V Rademakers, Hanna Briemberg, Dean J. Foti, Ian R. Mackenzie

Research output: Contribution to journalArticle

Abstract

Mutations in the TANK binding kinase 1 gene (TBK1) are associated with amyotrophic lateral sclerosis and/or frontotemporal dementia; however, the range of clinical phenotypes and neuropathological changes associated with these mutations have not yet been completely elucidated. We present the detailed clinical, neuroimaging, and neuropathological features of two brothers carrying the TBK1 p.Gly272_Thr331del mutation. Both presented with very similar and unusual clinical features including primary progressive aphasia and asymmetric-onset primary lateral sclerosis (PLS). Repeated electrophysiological studies failed to reveal any lower motor neuron involvement. Neuropathological evaluation of both cases revealed frontotemporal lobar degeneration with TDP-43 proteinopathy type B and selective involvement of upper motor neurons with TDP-43 inclusions. The stereotypical clinical presentation and neuropathological findings in these cases widen the phenotypic spectrum of TBK1 mutations and provide insights into the pathogenesis of PLS.

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Primary Progressive Aphasia
Motor Neuron Disease
Phosphotransferases
Mutation
Motor Neurons
Genes
TDP-43 Proteinopathies
Frontotemporal Lobar Degeneration
Neuroimaging
Phenotype

Keywords

  • neuropathology
  • primary lateral sclerosis
  • primary progressive aphasia
  • TBK1
  • TDP-43

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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Clinicopathologic correlations in a family with a TBK1 mutation presenting as primary progressive aphasia and primary lateral sclerosis. / Hirsch-Reinshagen, Veronica; Alfaify, Omar A.; Hsiung, Ging Yuek R.; Pottier, Cyril; Baker, Matt; Perkerson, Ralph B.; Rademakers, Rosa V; Briemberg, Hanna; Foti, Dean J.; Mackenzie, Ian R.

In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 01.01.2019.

Research output: Contribution to journalArticle

Hirsch-Reinshagen, Veronica ; Alfaify, Omar A. ; Hsiung, Ging Yuek R. ; Pottier, Cyril ; Baker, Matt ; Perkerson, Ralph B. ; Rademakers, Rosa V ; Briemberg, Hanna ; Foti, Dean J. ; Mackenzie, Ian R. / Clinicopathologic correlations in a family with a TBK1 mutation presenting as primary progressive aphasia and primary lateral sclerosis. In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2019.
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