Phenotypical difference of amyloid precursor protein (APP) V717L mutation in Japanese family.
BACKGROUND
Alzheimer's disease (AD) is the most common form of dementia. Mutations in genes such as those encoding amyloid precursor protein (APP), presenilin 1 and presenilin 2, are responsible for early-onset familial AD.


METHODS
In this study, we report a 275341 G > C (Val717Leu) mutation in the APP gene in a Japanese family with early onset AD by genetic screening. This mutation has previously been detected in European families. In the Japanese family we screened, the age at onset of AD was 47.1 ± 3.1 years old (n = 9; range, 42-52). The symptoms in the affected members included psychiatric vulnerability and focal signs such as pyramidal signs, epileptic seizures, and myoclonic discharges. An MR imaging study showed relatively mild atrophic changes in the bilateral hippocampus and cerebral cortices in all affected members compared with their clinical presentations.


CONCLUSIONS
We conclude that the clinical features of Alzheimer's disease can be different even when caused by the same mutation in the APP gene. Further clinical and genetic studies are required to clarify the relationship between phenotypes and genotypes.
Department of Neuropsychiatry, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Japan. masao-a@m.ehime-u.ac.jp
Masao
M
Abe
Naomi
N
Sonobe
Ryuji
R
Fukuhara
Yoko
Y
Mori
Shinichiro
S
Ochi
Teruhisa
T
Matsumoto
Takaaki
T
Mori
Satoshi
S
Tanimukai
Shu-ichi
S
Ueno
D000328:Adult; D000544:Alzheimer Disease / Q000151:congenital* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor