BACKGROUND/AIMS: Semantic dementia (SD) is a clinical subclassification of frontotemporal lobar degeneration. Patients with 'pure SD' present with semantic memory impairment preceding the frontal symptoms, and there have been no reports of familial cases. METHODS: We evaluated the clinical features of, and performed neuropsychological examinations on, the proband and two affected family members. Then we performed neuroimaging and genetic analysis of MAPT and other dementia-related genes in the proband. RESULTS: All three cases had semantic memory impairment with loss of word meanings as the primary early symptom. We diagnosed all cases as pure SD and identified a P301L mutation in the MAPT gene of the proband. CONCLUSION: Although the P301L mutation identified here has been previously described as pathogenic for frontotemporal dementia with parkinsonism-17 (FTDP-17), the proband and his two affected relatives showed different clinical symptoms from those of typical FTDP-17 cases who carry the P301L mutation. Pathologically, pure SD usually shows a TAR DNA-binding protein proteinopathy, but the molecular understanding of SD is not well established. Although our cases were clinically pure SD, the proband has a tau gene mutation, which would lead to tauopathy. These findings suggest that reconsideration of the molecular understanding of SD is warranted.
BACKGROUND/AIMS: Semantic dementia (SD) is a clinical subclassification of frontotemporal lobar degeneration. Patients with 'pure SD' present with semantic memory impairment preceding the frontal symptoms, and there have been no reports of familial cases. METHODS: We evaluated the clinical features of, and performed neuropsychological examinations on, the proband and two affected family members. Then we performed neuroimaging and genetic analysis of MAPT and other dementia-related genes in the proband. RESULTS: All three cases had semantic memory impairment with loss of word meanings as the primary early symptom. We diagnosed all cases as pure SD and identified a P301L mutation in the MAPT gene of the proband. CONCLUSION: Although the P301L mutation identified here has been previously described as pathogenic for frontotemporal dementia with parkinsonism-17 (FTDP-17), the proband and his two affected relatives showed different clinical symptoms from those of typical FTDP-17 cases who carry the P301L mutation. Pathologically, pure SD usually shows a TAR DNA-binding protein proteinopathy, but the molecular understanding of SD is not well established. Although our cases were clinically pure SD, the proband has a tau gene mutation, which would lead to tauopathy. These findings suggest that reconsideration of the molecular understanding of SD is warranted.
Authors: Gianluca Floris; Giuseppe Borghero; Antonino Cannas; Francesca Di Stefano; Maria R Murru; Daniela Corongiu; Stefania Cuccu; Stefania Tranquilli; Maria V Cherchi; Alessandra Serra; Gianluigi Loi; Maria G Marrosu; Adriano Chiò; Francesco Marrosu Journal: J Neurol Date: 2014-11-20 Impact factor: 4.849
Authors: Francesca Caso; Federica Agosta; Giuseppe Magnani; Rosalinda Cardamone; Valentina Borghesani; Zachary Miller; Nilo Riva; Renaud La Joie; Giovanni Coppola; Lea T Grinberg; William W Seeley; Bruce L Miller; Maria Luisa Gorno-Tempini; Massimo Filippi Journal: Brain Imaging Behav Date: 2020-04 Impact factor: 3.978
Authors: Yuying Liang; Elizabeth Gordon; Jonathan Rohrer; Laura Downey; Rohan de Silva; Hans Rolf Jäger; Jennifer Nicholas; Marc Modat; M Jorge Cardoso; Colin Mahoney; Jason Warren; Martin Rossor; Nick Fox; Diana Caine Journal: Neurocase Date: 2013-09-02 Impact factor: 0.881
Authors: Colin J Mahoney; Laura E Downey; Jon Beck; Yuying Liang; Simon Mead; Richard J Perry; Jason D Warren Journal: J Alzheimers Dis Date: 2013 Impact factor: 4.472