A novel presenilin 1 mutation resulting in familial Alzheimer's disease with an onset age of 29 years.
We have identified a novel Alzheimer's disease family in which affected subjects had a very young age of onset (range 29-35 years). Neuropathological confirmation of the diagnosis was obtained for one patient. Molecular analysis shows that within this family the disease results from a missense mutation at codon 235 of the presenilin 1 (PS-1) gene. Two patients had exhibited generalized tonico-clonic seizures several years before the onset of dementia. Whether this particular clinical feature is a consequence of the PS-1 mutation remains to be established. The Leu235Pro mutation is, to our knowledge, the PS-1 mutation associated with the youngest age of AD onset, which suggests that it has a drastic effect on PS-1 function.
Campion
D
D
Laboratoire de Génétique Moléculaire, CHU de Rouen, France.
Brice
A
A
Dumanchin
C
C
Puel
M
M
Baulac
M
M
De La Sayette
V
V
Hannequin
D
D
Duyckaerts
C
C
Michon
A
A
Martin
C
C
Moreau
V
V
Penet
C
C
Martinez
M
M
Clerget-Darpoux
F
F
Agid
Y
Y
Frebourg
T
T
D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D053764:Presenilin-1
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1