1. Novel GRN Mutations in Alzheimer's Disease and Frontotemporal Lobar Degeneration
- Author
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Cristiana Atzori, Benedetta Nacmias, Enrico Ghidoni, Luca Ambrogio, Daniele Imperiale, Irene Piaceri, Camilla Ferrari, Silvia Bagnoli, Sandro Sorbi, and Silvana Ungari
- Subjects
0301 basic medicine ,Proband ,Male ,Disease ,medicine.disease_cause ,Presenilin ,03 medical and health sciences ,0302 clinical medicine ,Progranulins ,Alzheimer Disease ,mental disorders ,medicine ,Amyloid precursor protein ,Dementia ,Humans ,Genetic Predisposition to Disease ,Genetics ,Mutation ,biology ,business.industry ,General Neuroscience ,General Medicine ,Frontotemporal lobar degeneration ,Middle Aged ,medicine.disease ,Pedigree ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,biology.protein ,Female ,Geriatrics and Gerontology ,Frontotemporal Lobar Degeneration ,business ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
Background During the twentieth century, frontotemporal dementia (FTD) was often misdiagnosed, confused with Alzheimer's disease or psychiatric disorders, jeopardizing care and research. Objective To analyze the FTD genes in the DNA samples of patients belonging to families clinically classified as probable Alzheimer's disease (FAD) in the early 1990s and not carrying mutation in the three main genes linked to FAD (Presenilin 1, Presenilin 2, and Amyloid precursor protein). Methods The genetic screening was performed on 63 probands diagnosed as FAD before the early 2000s. Results Four patients out of the 63 studied (4/63, 6.3%) resulted as carrying four different GRN genetic variations: p.T272SfsX10, p.R110X, p.C149LfsX10, and p.W304C. The first two mutations (p.T272SfsX10, p.R110X) are the most frequent ones in Italy in FTD patients; the latter two (p.C149LfsX10 and p.W304C) are not described in the scientific literature. Conclusion Our data suggest that it can be important to re-examine FAD patients diagnosed when the FTD spectrum was not well recognized and the causative FTD genes had not yet been identified. Moreover, we propose initially analyzing genes associated with the first form of suspected dementia and, if the results are negative, studying genes implicated in the other form of dementia.
- Published
- 2018