Genetic screening of ANXA11 revealed novel mutations linked to Amyotrophic Lateral Sclerosis
Résumé
ANXA11 mutations have previously been discovered in Amyotrophic Lateral Sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome dataset obtained from 330 French patients, including 150 familial ALS (FALS) index cases and 180 sporadic (SALS) cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.L254V variant was associated to early onset SALS. The novel p.D40Y mutation and the p.G38R variant concerned patients with predominant pyramidal tract involvement and cognitive decline. Neuropathological findings in a p.G38R carrier associated the presence of ALS typical inclusions within the spinal cord, massive degeneration of the lateral tracts and type A Frontotemporal Lobar degeneration (FTLD). This mutant form of Annexin A11 accumulated in various brain regions and in spinal cord motor neurons, although its stability was decreased in patients' lymphoblasts. Since most ANXA11 inclusions were not colocalized with TDP-43 or p62 deposits, ANXA11 aggregation does not seem mandatory to trigger neurodegeneration with additional participants/partner proteins that could intervene.
Domaines
Neurosciences [q-bio.NC]
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Teyssou et al. - 2021 - Genetic screening of ANXA11 revealed novel mutatio.pdf (730.25 Ko)
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