Somatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer's disease
- Nicolas, Gaël
- Acuna-Hidalgo, Rocio
- Keogh, Michael
- Quenez, Olivier
- Steehouwer, Marloes
- Lelieveld, Stefan, H.
- Rousseau, Stéphane
- Richard, Anne-Claire
- Oud, Manon
- Marguet, Florent
- Laquerrière, Annie
- Morris, Chris
- Attems, Johannes
- Smith, Colin
- Ansorge, Olaf
- Al Sarraj, Safa
- Frebourg, Thierry
- Campion, Dominique
- Hannequin, Didier
- Wallon, David
- Gilissen, Christian
- Chinnery, Patrick
- Veltman, Joris, A
- Hoischen, Alexander
DOIAbstract
International audienceIntroductionA minority of patients with sporadic early‐onset Alzheimer's disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes such as APP PSEN1 , or PSEN2 . We hypothesized that negatively screened patients may harbor somatic variants in these genes.MethodsWe applied an ultrasensitive approach based on single‐molecule molecular inversion probes followed by deep next generation sequencing of 11 genes to 100 brain and 355 blood samples from 445 sporadic patients with AD (>80% exhibited an early onset, <66 years).ResultsWe identified and confirmed nine somatic variants (allele fractions: 0.2%–10.8%): two APP , five SORL1 , one NCSTN , and one MARK4 variants by independent amplicon‐based deep se...
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