, ANR-10-IAIHU-06. This work was partially funded by the Program Hospitalier de Recherche Clinique FTLD-exome (to ILB., promotion Assistance PubliqueeHôpitaux de Paris) and by the ANR-PRTS PREV-DEMALS project (to ILB

M. Ceccaldi, Philippe Couratier, Frédéric Blanc (Hôpitaux Civils, Strasbourg), Claire Bouteleau-Bretonnière

. Mathieu-chastan, Marie Chupin (CATI, ICM, Paris), Olivier Colliot, Stéphane Lehéricy (Hôpital Pitié-Salpêtrière Salpêtrière

M. Barbier, A. Camuzat, M. Houot, F. Clot, P. Caroppo et al., Factors influencing the age at onset in familial frontotemporal lobar dementia: important weight of genetics, French Clinical and Genetic Research Network on FTD/FTD-ALS, Predict-PGRN & PrevDemAls Study Groups, 2017.

J. Beck, M. Poulter, D. Hensman, J. D. Rohrer, C. J. Mahoney et al., Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population, Am. J. Hum. Genet, vol.92, pp.345-353, 2013.

M. Cruts, I. Gijselinck, T. Van-langenhove, J. Van-der-zee, and C. Van-broeckhoven, Current insights into the C9orf72 repeat expansion diseases of the FTLD/ ALS spectrum, Trends Neurosci, vol.36, pp.450-459, 2013.

M. Dejesus-hernandez, I. R. Mackenzie, B. F. Boeve, A. L. Boxer, M. Baker et al., GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS, vol.72, pp.245-256, 2011.

O. Dols-icardo, A. García-redondo, R. Rojas-garcía, R. Sánchez-valle, A. Noguera et al., Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia, Hum. Mol. Genet, vol.23, pp.749-754, 2014.

C. J. Donnelly, P. Zhang, J. T. Pham, A. R. Haeusler, A. R. Heusler et al., RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention, Neuron, vol.80, pp.415-428, 2013.

I. Gijselinck, S. Van-mossevelde, J. Van-der-zee, A. Sieben, S. Engelborghs et al., The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter, Mol. Psychiatry, vol.21, 2016.

J. Jiang, Q. Zhu, T. F. Gendron, S. Saberi, M. Mcalonis-downes et al., Neuron, vol.90, pp.535-550, 2016.

C. Lagier-tourenne, M. Baughn, F. Rigo, S. Sun, P. Liu et al., Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration, Proc. Natl. Acad. Sci. U. S. A, vol.110, pp.4530-4539, 2013.

L. Ber, I. Camuzat, A. Guillot-noel, L. Hannequin, D. Lacomblez et al., C9ORF72 repeat expansions in the frontotemporal dementias spectrum of diseases: a flow-chart for genetic testing, J. Alzheimers Dis, vol.34, pp.485-499, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00924796

E. Majounie, A. E. Renton, K. Mok, E. G. Dopper, A. Waite et al., Lancet Neurol, vol.11, pp.323-330, 2012.

A. Nordin, C. Akimoto, A. Wuolikainen, H. Alstermark, P. Jonsson et al., Extensive size variability of the GGGGCC expansion in C9orf72 in both neuronal and non-neuronal tissues in 18 patients with ALS or FTD, Hum. Mol. Genet, vol.24, pp.3133-3142, 2015.

A. E. Renton, E. Majounie, A. Waite, J. Simón-sánchez, S. Rollinson et al., , pp.257-268, 2011.

J. Russ, E. Y. Liu, K. Wu, D. Neal, E. Suh et al., Hypermethylation of repeat expanded C9orf72 is a clinical and molecular disease modifier, Acta Neuropathol. (Berl.), vol.129, pp.39-52, 2015.

E. Suh, E. B. Lee, D. Neal, E. M. Wood, J. B. Toledo et al., Semi-automated quantification of C9orf72 expansion size reveals inverse correlation between hexanucleotide repeat number and disease duration in frontotemporal degeneration, Acta Neuropathol. (Berl.), vol.130, pp.978-988, 2013.

S. Van-mossevelde, J. Van-der-zee, I. Gijselinck, K. Sleegers, J. De-bleecker et al., Clinical evidence of disease anticipation in families segregating a C9orf72 repeat expansion, JAMA Neurol, vol.74, pp.445-452, 2017.

Z. Xi, L. Zinman, D. Moreno, J. Schymick, Y. Liang et al., Hypermethylation of the CpG island near the G4C2 repeat in ALS with a C9orf72 expansion, Am. J. Hum. Genet, vol.92, pp.981-989, 2013.