1. Frontotemporal dementia spectrum: first genetic screen in a Greek cohort
- Author
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Dimitrios Agiomyrgiannakis, Stavroula Matsi, Eliana Marisa Ramos, Christos Koros, Leonidas Stefanis, Anastasios Bonakis, Chryseis Florou-Hatziyiannidou, Deepika Dokuru, Kevin Wojta, Q. Wang, Vasiliki Papastefanopoulou, Stella Fragkiadaki, Vasiliki Kamtsadeli, John Papatriantafyllou, Maria Stamelou, Ion Beratis, Victoria Van Berlo, Sokratis G. Papageorgiou, Bruce L. Miller, Giovanni Coppola, Suzee E. Lee, Nikolaos Andronas, Dionysia Kontaxopoulou, Niki Tsinia, Christos Kroupis, and Alden Y. Huang
- Subjects
Male ,0301 basic medicine ,Aging ,Biology ,TARDBP ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,C9orf72 ,mental disorders ,PSEN1 ,medicine ,Humans ,Dementia ,Genetic Predisposition to Disease ,Genetic Testing ,Amyotrophic lateral sclerosis ,Genetic Association Studies ,Genetics ,DNA Repeat Expansion ,C9orf72 Protein ,Greece ,General Neuroscience ,Amyotrophic Lateral Sclerosis ,medicine.disease ,030104 developmental biology ,Frontotemporal Dementia ,Mutation ,Cohort ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,030217 neurology & neurosurgery ,Developmental Biology ,Frontotemporal dementia ,Genetic screen - Abstract
Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative syndromes associated with several causative and susceptibility genes. Herein, we aimed to determine the incidence of the most common causative dementia genes in a cohort of 118 unrelated Greek FTD spectrum patients. We also screened for novel possible disease-associated variants in additional 21 genes associated with FTD or amyotrophic lateral sclerosis. Pathogenic or likely pathogenic variants were identified in 16 cases (13.6%). These included repeat expansions in C9orf72 and loss-of-function GRN variants, and likely pathogenic variants in TARDBP, MAPT, and PSEN1. We also identified 14 variants of unknown significance in other rarer FTD or amyotrophic lateral sclerosis genes that require further segregation and functional analysis. Our genetic screen revealed a high genetic burden in familial Greek FTD cases (30.4%), whereas only two of the sporadic cases (3.5%) carried a likely pathogenic variant. A substantial number of familial cases still remain without an obvious causal variant, suggesting the existence of other FTD genetic causes besides those currently screened in clinical routine.
- Published
- 2019