Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers.

Neurobiol Aging

Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière ICM, Hôpital Pitié-Salpêtrière, Paris, France; National Reference Center for Rare or Early Dementias, Institute of Memory and Alzheimer's Disease IM2A, Department of Neurology, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France. Electronic address:

Published: February 2019

A (GGGGCC) 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) but our results suggested that the association was mainly driven by age at collection (p < 10). 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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2018.09.010DOI Listing

Publication Analysis

Top Keywords

age collection
12
repeats number
12
presymptomatic carriers
8
ftd als
8
age
5
relations c9orf72
4
expansion
4
c9orf72 expansion
4
expansion size
4
size blood
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!