Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation.
BACKGROUND
Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features.


RESULTS
We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation).


CONCLUSIONS
The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations.
Lindquist
Suzanne Granhøj
SG
Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. suzanne.lindquist@rh.regionh.dk
Nielsen
Jørgen Erik
JE
Stokholm
Jette
J
Schwartz
Marianne
M
Batbayli
Mustafa
M
Ballegaard
Martin
M
Erdal
Jesper
J
Krabbe
Katja
K
Waldemar
Gunhild
G
D000409:Alanine / Q000235:genetics; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001794:Blood Pressure; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D005192:Family Health; D006801:Humans; D007492:Iran / Q000208:ethnology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D013912:Threonine / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D013912:Threonine; D000409:Alanine