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.
Laboratoire de Génétique Moléculaire, CHU de Rouen, France.
D
D
Campion
A
A
Brice
C
C
Dumanchin
M
M
Puel
M
M
Baulac
V
V
De La Sayette
D
D
Hannequin
C
C
Duyckaerts
A
A
Michon
C
C
Martin
V
V
Moreau
C
C
Penet
M
M
Martinez
F
F
Clerget-Darpoux
Y
Y
Agid
T
T
Frebourg
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