Incomplete penetrance in familial Alzheimer’s disease with PSEN1 Ala260Gly mutation
- Resource Type
- Authors
- Giulia Vinceti; Siro Bagnoli; Chiara Galli; Sandro Sorbi; Benedetta Nacmias; Camilla Ferrari; Annalisa Chiari; Irene Piaceri; Maria Angela Molinari; S. Trujillo Saavedra
- Source
- Neurological Sciences. 41:2263-2266
- Subject
- Male
Penetrance
Dermatology
Disease
Biology
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
Presenilin-1
PSEN1
Humans
030212 general & internal medicine
Epigenetics
Age of Onset
Cognitive reserve
Genetics
Genetic heterogeneity
General Medicine
Middle Aged
Psychiatry and Mental health
Mutation
DNA methylation
Mutation (genetic algorithm)
Female
Neurology (clinical)
030217 neurology & neurosurgery
- Language
- ISSN
- 1590-3478
1590-1874
Presenilin1 (PSEN1) gene is the most common known genetic cause of early-onset familial Alzheimer's disease. We describe an Italian family with the known p.Ala260Gly mutation in PSEN1 gene. The presence of an asymptomatic 64-year-old male carrying the mutation provides evidence of a possible incomplete penetrance leading to a wider range of age at onset. In order to evaluate whether or not epigenetic modifications could contribute to the phenotypic heterogeneity, we assessed global DNA methylation levels which resulted significantly higher in the three females than in their presymptomatic brother. The study suggests that DNA methylation can contribute to slowing down or possibly protecting from the manifestation of symptoms even in monogenic diseases, emphasizing the great complexity of familial Alzheimer's disease.