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Article Dans Une Revue Molecular Psychiatry Année : 2012

High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.

D. Hannequin
  • Fonction : Auteur
S. Coutant
  • Fonction : Auteur
A. Rovelet-Lecrux
D. Wallon
  • Fonction : Auteur
S. Rousseau
  • Fonction : Auteur
S. Legallic
  • Fonction : Auteur
C. Thomas-Anterion
  • Fonction : Auteur
F. Etcharry-Bouyx
  • Fonction : Auteur
C. Berr
  • Fonction : Auteur
P. Amouyel
  • Fonction : Auteur
H. Dauchel
  • Fonction : Auteur
Claire Boutoleau-Bretonnière
  • Fonction : Auteur
  • PersonId : 1290711
  • IdRef : 073681458
C. Thauvin
  • Fonction : Auteur
T. Frebourg
  • Fonction : Auteur
Non Renseigné
  • Fonction : Auteur

Résumé

Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD.

Dates et versions

hal-00965204 , version 1 (24-03-2014)

Identifiants

Citer

Corinne Pottier, D. Hannequin, S. Coutant, A. Rovelet-Lecrux, D. Wallon, et al.. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.. Molecular Psychiatry, 2012, 17 (9), pp.875-9. ⟨10.1038/mp.2012.15⟩. ⟨hal-00965204⟩
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