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C9orf72 Repeat Expansions in Rapid Eye Movement Sleep Behaviour Disorder

  • Hussein Daoud (a1), Ronald B. Postuma (a2) (a3), Cynthia V. Bourassa (a1), Daniel Rochefort (a1), Maude Turcotte Gauthier (a1), Jacques Montplaisir (a3), Jean-Francois Gagnon (a2) (a4), Isabelle Arnulf (a5), Yves Dauvilliers (a6), Christelle Monaca Charley (a7), Yuichi Inoue (a8), Taeko Sasai (a8), Birgit Högl (a9), Alex Desautels (a2), Birgit Frauscher (a9), Valérie Cochen De Cock (a3), Guy A. Rouleau (a1) and Patrick A. Dion (a1) (a10)...

Abstract

Background : A large hexanucleotide repeat expansion in C9orf72 has been identified as the most common genetic cause in familial amyotrophic lateral sclerosis and frontotemporal dementia. Rapid Eye Movement Sleep Behavior Disorder (RBD) is a sleep disorder that has been strongly linked to synuclein-mediated neurodegeneration. The aim of this study was to evaluate the role of the C9orf72 expansions in the pathogenesis of RBD. Methods: We amplified the C9orf72 repeat expansion in 344 patients with RBD by a repeat-primed polymerase chain reaction assay. Results : We identified two RBD patients carrying the C9orf72 repeat expansion. Most interestingly, these patients have the same C9orf72 associated-risk haplotype identified in 9p21-linked amyotrophic lateral sclerosis and frontotemporal dementia families. Conclusions : Our study enlarges the phenotypic spectrum associated with the C9orf72 hexanucleotide repeat expansions and suggests that, although rare, this expansion may play a role in the pathogenesis of RBD.

Expansion des répétitions de C9orf72 dans le trouble des conduites du sommeil paradoxal. Contexte: Une importante expansion de la répétition de l’hexanucléotide C9orf72 a été identifiée comme la cause génétique la plus fréquente de la sclérose latérale amyotrophique familiale et de la démence fronto-temporale. Le trouble des conduites du sommeil paradoxal est un trouble du sommeil qui a été fortement associé à une neurodégénérescence médiée par la synucléine. L’objectif de cette étude était d’évaluer le rôle des expansions de C9orf72 dans la pathogénie des troubles du sommeil paradoxal. Méthodes: Nous avons amplifié l’expansion des répétitions de C9orf72 chez 344 patients atteints de troubles du sommeil paradoxal au moyen d’une réaction en chaîne de la polymérase amorcée par la répétition. Résultats: Nous avons identifié deux patients atteints de troubles du sommeil paradoxal porteurs de l’expansion des répétitions de C9orf72. Il a été extrêmement intéressant de constater que ces patients présentaient le même haplotype de risque associé à C9orf72 dans les familles atteintes de sclérose latérale amyotrophique et de démence fronto-temporale liées à 9p21. Conclusions: Notre étude élargit le spectre des phénotypes associés à l’expansion des répétitions de l’hexanucléotide C9orf72 et suggère que, bien que rare, cette expansion pourrait jouer un rôle dans la pathogénie des troubles du sommeil paradoxal.

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Copyright

Corresponding author

Correspondence to: Guy A. Rouleau, Montreal Neurological Institute, 3801 rue University, Montreal, H3A 2B4, Quebec, Canada. Email: guy.rouleau@mcgill.ca.

References

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