Novel mutations and repeated findings of mutations in familial Alzheimer disease.
Twenty-one unrelated patients with a history of suspected familial Alzheimer disease (FAD) were screened for mutations in PSEN1, PSEN2, and APP, the known FAD genes encoding the presenilins (PS1 and PS2) and the amyloid precursor protein (APP). The mutation detection rate was 57%. Of the nine pathogenic mutations found in 12 cases, three were in APP, one in PSEN2, and five in PSEN1, including two novel Greek mutations (L113Q and N135S). Whereas our findings suggest the possibility of single founders for the majority of mutations, we found evidence of recurrence of the APP mutations V717L and V717I.
Finckh
Ulrich
U
Institute of Human Genetics, University Hospital Hamburg-Eppendorf, University of Hamburg, Butenfeld 42, 22529 Hamburg, Germany. finckh@uke.uni-hamburg.de
Kuschel
Christian
C
Anagnostouli
Maria
M
Patsouris
Efstratios
E
Pantes
George V
GV
Gatzonis
Stylianos
S
Kapaki
Elisabeth
E
Davaki
Panagiota
P
Lamszus
Katrin
K
Stavrou
Dimitrios
D
Gal
Andreas
A
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D005192:Family Health; D005260:Female; D018703:Founder Effect; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D053764:Presenilin-1; D053766:Presenilin-2
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2