Semantic and nonfluent aphasic variants, secondarily associated with amyotrophic lateral sclerosis, are predominant frontotemporal lobar degeneration phenotypes in TBK1 carriers

Paola Caroppo, Agnès Camuzat, Anne De Septenville, Philippe Couratier, Lucette Lacomblez, Sophie Auriacombe, Olivier Flabeau, Ludmila Jornéa, Frederic Blanc, François Sellal, Benjamin Cretin, Vincent Meininger, Marie Céline Fleury, Philippe Couarch, Bruno Dubois, Alexis Brice, Isabelle Le Ber

Research output: Contribution to journalArticle

Abstract

Introduction: TBK1 mutations represent a rare novel genetic cause of amyotrophic lateral sclerosis (ALS) without or with dementia. The full spectrum of TBK1 phenotypes has not been completely defined so far. Methods: We describe the clinical and neuroimaging characteristics of loss-of-function mutation carriers initially presenting with frontotemporal lobar degeneration (FTLD) phenotypes. Results: Two carriers initially presented semantic variant of FTLD (svFTLD); two other developed nonfluent variant of FTLD (nfvFTLD) and corticobasal syndrome (CBS), associated with severe anterior temporal and opercular atrophy. All secondarily developed ALS. Discussion: This study enlarges the phenotypic spectrum of TBK1 mutations, including svFTLD and nfvFTLD/CBS, not reported so far. Aphasic presentations seem to be more evocative of TBK1 genotype than behavioral variant of FTLD, and TBK1 should be analyzed in patients with isolated FTLD at onset, particularly in rare aphasic cases secondarily associated with ALS.

Original languageEnglish
Pages (from-to)481-486
Number of pages6
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume1
Issue number4
DOIs
Publication statusPublished - Dec 1 2015

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Frontotemporal Lobar Degeneration
Amyotrophic Lateral Sclerosis
Semantics
Phenotype
Mutation
Neuroimaging
Atrophy
Dementia
Genotype

Keywords

  • Amyotrophic lateral sclerosis
  • Aphasic variant FTLD
  • Behavioral disorders
  • Frontotemporal lobar degeneration
  • Genetics
  • Semantic variant FTLD
  • TBK1

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Neurology

Cite this

Semantic and nonfluent aphasic variants, secondarily associated with amyotrophic lateral sclerosis, are predominant frontotemporal lobar degeneration phenotypes in TBK1 carriers. / Caroppo, Paola; Camuzat, Agnès; De Septenville, Anne; Couratier, Philippe; Lacomblez, Lucette; Auriacombe, Sophie; Flabeau, Olivier; Jornéa, Ludmila; Blanc, Frederic; Sellal, François; Cretin, Benjamin; Meininger, Vincent; Fleury, Marie Céline; Couarch, Philippe; Dubois, Bruno; Brice, Alexis; Le Ber, Isabelle.

In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, Vol. 1, No. 4, 01.12.2015, p. 481-486.

Research output: Contribution to journalArticle

Caroppo, P, Camuzat, A, De Septenville, A, Couratier, P, Lacomblez, L, Auriacombe, S, Flabeau, O, Jornéa, L, Blanc, F, Sellal, F, Cretin, B, Meininger, V, Fleury, MC, Couarch, P, Dubois, B, Brice, A & Le Ber, I 2015, 'Semantic and nonfluent aphasic variants, secondarily associated with amyotrophic lateral sclerosis, are predominant frontotemporal lobar degeneration phenotypes in TBK1 carriers', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, vol. 1, no. 4, pp. 481-486. https://doi.org/10.1016/j.dadm.2015.10.002
Caroppo, Paola ; Camuzat, Agnès ; De Septenville, Anne ; Couratier, Philippe ; Lacomblez, Lucette ; Auriacombe, Sophie ; Flabeau, Olivier ; Jornéa, Ludmila ; Blanc, Frederic ; Sellal, François ; Cretin, Benjamin ; Meininger, Vincent ; Fleury, Marie Céline ; Couarch, Philippe ; Dubois, Bruno ; Brice, Alexis ; Le Ber, Isabelle. / Semantic and nonfluent aphasic variants, secondarily associated with amyotrophic lateral sclerosis, are predominant frontotemporal lobar degeneration phenotypes in TBK1 carriers. In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. 2015 ; Vol. 1, No. 4. pp. 481-486.
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AU - Couratier, Philippe

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AU - Cretin, Benjamin

AU - Meininger, Vincent

AU - Fleury, Marie Céline

AU - Couarch, Philippe

AU - Dubois, Bruno

AU - Brice, Alexis

AU - Le Ber, Isabelle

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AB - Introduction: TBK1 mutations represent a rare novel genetic cause of amyotrophic lateral sclerosis (ALS) without or with dementia. The full spectrum of TBK1 phenotypes has not been completely defined so far. Methods: We describe the clinical and neuroimaging characteristics of loss-of-function mutation carriers initially presenting with frontotemporal lobar degeneration (FTLD) phenotypes. Results: Two carriers initially presented semantic variant of FTLD (svFTLD); two other developed nonfluent variant of FTLD (nfvFTLD) and corticobasal syndrome (CBS), associated with severe anterior temporal and opercular atrophy. All secondarily developed ALS. Discussion: This study enlarges the phenotypic spectrum of TBK1 mutations, including svFTLD and nfvFTLD/CBS, not reported so far. Aphasic presentations seem to be more evocative of TBK1 genotype than behavioral variant of FTLD, and TBK1 should be analyzed in patients with isolated FTLD at onset, particularly in rare aphasic cases secondarily associated with ALS.

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