TY - JOUR
T1 - Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers
AU - Sabatelli, Mario
AU - Lattante, Serena
AU - Fournier, Clémence
AU - Barbier, Mathieu
AU - Camuzat, Agnès
AU - Anquetil, Vincent
AU - Clot, Fabienne
AU - Cazeneuve, Cécile
AU - Rinaldi, Daisy
AU - Couratier, Philippe
AU - Deramecourt, Vincent
AU - Belliard, Serge
AU - Vercelletto, Martine
AU - Forlani, Sylvie
AU - Jornea, Ludmila
AU - Brice, Alexis
AU - Auriacombe, Sophie
AU - Blanc, Frédéric
AU - Bouteleau-Bretonnière, Claire
AU - Ceccaldi, Mathieu
AU - Didic, Mira
AU - Dubois, Bruno
AU - Duyckaerts, Charles
AU - Etcharry-Bouix, Frédérique
AU - Golfier, Véronique
AU - Hannequin, Didier
AU - Lacomblez, Lucette
AU - Le Ber, Isabelle
AU - Levy, Richard
AU - Michel, Bernard-François
AU - Pasquier, Florence
AU - Thomas-Anterion, Catherine
AU - Pariente, Jérémie
AU - Sellal, François
AU - Benchetrit, Eve
AU - Bertin, Hugo
AU - Bertrand, Anne
AU - Bissery, Anne
AU - Bombois, Stéphanie
AU - Boncoeur, Marie-Paule
AU - Cassagnaud, Pascaline
AU - Chastan, Mathieu
AU - Chen, Yaohua
AU - Chupin, Marie
AU - Colliot, Olivier
AU - Delbeucq, Xavier
AU - Delmaire, Christine
AU - Gerardin, Emmanuel
AU - Hossein-Foucher, Claude
AU - Habert, Marie-Odile
AU - Lautrette, Géraldine
AU - Lebouvier, Thibaud
AU - Lehéricy, Stéphane
AU - Le Toullec, Benjamin
AU - Martineau, Kelly
AU - Mackowiak, Marie-Anne
AU - Monteil, Jacques
AU - Petyt, Grégory
AU - Pradat, Pierre-François
AU - Oya, Assi-Hervé
AU - Rollin-Sillaire, Adeline
AU - Salachas, François
AU - Sayah, Sabrina
AU - Wallon, David
AU - Leguern, Eric
PY - 2019
Y1 - 2019
N2 - A (GGGGCC) n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10 e−4 ) but our results suggested that the association was mainly driven by age at collection (p < 10 e−4 ). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers.
AB - A (GGGGCC) n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10 e−4 ) but our results suggested that the association was mainly driven by age at collection (p < 10 e−4 ). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers.
KW - Amyotrophic Lateral sclerosis
KW - Anticipation
KW - C9orf72
KW - Frontotemporal dementia
KW - Frontotemporal lobar degeneration
KW - TDP-43
KW - Amyotrophic Lateral sclerosis
KW - Anticipation
KW - C9orf72
KW - Frontotemporal dementia
KW - Frontotemporal lobar degeneration
KW - TDP-43
UR - http://hdl.handle.net/10807/139948
UR - http://www.elsevier.com/locate/neuaging
U2 - 10.1016/j.neurobiolaging.2018.09.010
DO - 10.1016/j.neurobiolaging.2018.09.010
M3 - Article
VL - 74
SP - 234-234.e8
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -