Octapeptide repeat insertions in the prion protein gene and early onset dementia.
OBJECTIVE
The most common familial early onset dementia mutations are found in the genes involved in Alzheimer's disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved.


METHODS
Following identification of a two-octapeptide repeat insertion in PRNP, we conducted a meta-analysis to investigate the relation of number of PRNP octapeptide repeats with age at disease onset and duration of illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used a linear mixed effects model to assess the relation of number of repeats with age at disease onset, and studied the effect of the number of inserted octapeptide repeats on disease duration with a Cox proportional hazards regression analysis.


RESULTS
We found an increasing number of repeats associated with younger age at onset (p < 0.001). Duration of the disease decreased significantly with the length of the octapeptide repeat (p < 0.001) when adjusting for age at onset.


CONCLUSIONS
Our findings show significant inverse associations of the length of the PRNP octapeptide repeat with age at disease onset and disease duration in the spongiform encephalopathies.
Croes
E A
EA
Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
Theuns
J
J
Houwing-Duistermaat
J J
JJ
Dermaut
B
B
Sleegers
K
K
Roks
G
G
Van den Broeck
M
M
van Harten
B
B
van Swieten
J C
JC
Cruts
M
M
Van Broeckhoven
C
C
van Duijn
C M
CM
D017668:Age of Onset; D003704:Dementia / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D010641:Phenotype; D011328:Prions / Q000235:genetics*; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid; D013997:Time Factors
D011328:Prions