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.