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Article Dans Une Revue European Journal of Human Genetics Année : 2024

Upstream open reading frame-introducing variants in patients with primary familial brain calcification

Olivier Quenez
Wandrille Delcroix
Alice Rucar
  • Fonction : Auteur

Résumé

SORL1 loss of function is associated with Alzheimer’s disease (AD) risk through increased Aβ peptide secretion. We expressed 10 maturation-defective rare missense SORL1 variants in HEK cells and showed that decreasing growing temperature led to a significant increase in the maturation of the encoded protein SorLA for 6/10. In edited hiPSC carrying two of these variants, maturation of the protein was restored partially by decreasing the culture temperature and was associated with concomitant decrease in Aβ secretion. Correcting SorLA maturation in the context of maturation-defective missense variants could thus be a relevant strategy to improve SorLA protective function against AD.
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Dates et versions

hal-04659594 , version 1 (23-07-2024)

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Citer

Anne Rovelet-Lecrux, Antoine Bonnevalle, Olivier Quenez, Wandrille Delcroix, Kévin Cassinari, et al.. Upstream open reading frame-introducing variants in patients with primary familial brain calcification. European Journal of Human Genetics, 2024, 32 (7), pp.779-785. ⟨10.1038/s41431-024-01580-4⟩. ⟨hal-04659594⟩
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