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.
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 FTDpatients; 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 FADpatients 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.
Authors: Badri N Vardarajan; Dolly Reyes-Dumeyer; Angel L Piriz; Rafael A Lantigua; Martin Medrano; Diones Rivera; Ivonne Z Jiménez-Velázquez; Eden Martin; Margaret A Pericak-Vance; William Bush; Lindsay Farrer; Jonathan L Haines; Li-San Wang; Yuk Yee Leung; Gerard Schellenberg; Walter Kukull; Philip De Jager; David A Bennett; Julie A Schneider; Richard Mayeux Journal: Alzheimers Dement Date: 2022-02-09 Impact factor: 16.655
Authors: Denis A Baird; Jimmy Z Liu; Jie Zheng; Solveig K Sieberts; Thanneer Perumal; Benjamin Elsworth; Tom G Richardson; Chia-Yen Chen; Minerva M Carrasquillo; Mariet Allen; Joseph S Reddy; Philip L De Jager; Nilufer Ertekin-Taner; Lara M Mangravite; Ben Logsdon; Karol Estrada; Philip C Haycock; Gibran Hemani; Heiko Runz; George Davey Smith; Tom R Gaunt Journal: PLoS Genet Date: 2021-01-08 Impact factor: 5.917