High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.
Mol Psychiatry
; 17(9): 875-9, 2012 Sep.
Article
in En
| MEDLINE
| ID: mdl-22472873
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Membrane Transport Proteins
/
Codon, Nonsense
/
Mutation, Missense
/
LDL-Receptor Related Proteins
/
Alzheimer Disease
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
Mol Psychiatry
Journal subject:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Year:
2012
Document type:
Article
Affiliation country:
France