title: Different clinical phenotypes in siblings with a presenilin-1 P264L mutation.
abstract: BACKGROUND
  Mutations in the presenilin-1 gene (PSEN1) have been identified in autosomal dominant early-onset cases of Alzheimer's disease (AD).
  
  
  OBJECTIVE
  To investigate different clinical phenotypes of siblings possessing the same heterozygous P264L mutation in the PSEN1 gene.
  
  
  METHODS
  We evaluated clinical features, neuroimaging results, and neuropsychological examinations. The PSEN1 gene and other dementia-related gene mutations were screened.
  
  
  RESULTS
  We clinically diagnosed the proband as atypical AD with frontotemporal dementia features and diagnosed the elder brother of the proband as typical AD, based on neuropsychological symptoms and a brain imaging examination including amyloid imaging data. A heterozygous P264L mutation in the PSEN1 gene was identified in both siblings.
  
  
  CONCLUSIONS
  This study is one of few reports of AD siblings possessing the same mutation but exhibiting different clinical phenotypes in a Japanese family possessing a P264L mutation in the PSEN1 gene. The current results suggest that unknown modifiers, including both genetic and epigenetic factors, may alter the pathological and clinical phenotypes of a genetically predetermined disease.
authors.affiliation: Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mio
authors.initials: M
authors.lastname: Ichiba
authors.forename: Seigo
authors.initials: S
authors.lastname: Fujita
authors.forename: Kouzo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Sano
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D056344:Executive Function; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D059647:Gene-Environment Interaction; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D016743:Mental Competency; D008875:Middle Aged; D009154:Mutation; D059906:Neuroimaging / Q000379:methods; D009483:Neuropsychological Tests; D010375:Pedigree; D053764:Presenilin-1 / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D035781:Siblings / Q000523:psychology
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1