Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease.
OBJECTIVE
To describe a novel missense mutation, Asp678Asn (D678N), in the amyloid precursor protein (APP) gene in a Japanese pedigree of probable familial Alzheimer's disease (FAD).


METHODS
The proband was a women of 72. Symptoms of dementia that fulfilled the criteria for probable Alzheimer's disease appeared at about 60 years of age, and slowly worsened over more than 10 years without evident cerebrovascular complications, either clinically or neuroradiologically.


METHODS
Polymerase chain reaction single strand conformational polymorphism (PCR-SSCP) analysis followed by sequence analysis was used to examine genomic DNA of the proband for mutations in the APP gene exons 16 and 17.


RESULTS
Analysis of the APP exon 16 in the proband showed a GAC to AAC nucleotide substitution in codon 678 of the APP gene, causing an amino acid substitution of Asp to Asn (D678N). Heterozygosity of the APP D678N mutation was found in the proband and in the demented elder sister.


CONCLUSIONS
The production and accumulation of mutated Abeta (Asn7-Abeta) or the misfunction of D678N mutant APP may have pathogenic properties for the development of Alzheimer's disease in this pedigree.
Wakutani
Y
Y
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan. ywzku@grape.med.tottori-u.ac.jp
Watanabe
K
K
Adachi
Y
Y
Wada-Isoe
K
K
Urakami
K
K
Ninomiya
H
H
Saido
T C
TC
Hashimoto
T
T
Iwatsubo
T
T
Nakashima
K
K
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis; D005091:Exons; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009483:Neuropsychological Tests; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015899:Tomography, Emission-Computed, Single-Photon
D002352:Carrier Proteins