title: Clinical phenotype of G206D mutation in the presenilin 1 gene in pathologically confirmed familial Alzheimer's disease.
abstract: Familial Alzheimer's disease (FAD) is genetically heterogeneous, autosomal dominant, with nearly 100% penetrance. In FAD, most common causative genetic mutations are presenilin 1 (PSEN1), presenilin 2 and amyloid-β protein precursor. We demonstrate a family presenting as early-onset AD with a rapid deterioration course and seizure developed after 1.5 years of symptoms. A histopathological examination of the frontal cortex showed amyloid deposition and abundant phosphorylated tau deposition. In both cases, a single nucleotide mutation from guanine to adenine at exon 7 was found in PSEN1 (c.617G>A, codon change from GGT to GAT). Though G206D mutation in PSEN1 gene was found in FAD, no clinical phenotype or pathological finding was documented. This is the first report of PSEN1 mutation (Gly206Asp) with features of seizure and a rapid progressive cognitive decline in a pathologically confirmed case of FAD.
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ya-Ying
authors.initials: YY
authors.lastname: Wu
authors.forename: Irene Han-Juo
authors.initials: IH
authors.lastname: Cheng
authors.forename: Chin-Cheng
authors.initials: CC
authors.lastname: Lee
authors.forename: Ming-Jang
authors.initials: MJ
authors.lastname: Chiu
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Ta-Fu
authors.initials: TF
authors.lastname: Chen
authors.forename: Jung-Lung
authors.initials: JL
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D019943:Amino Acid Substitution / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1