title: Genetics of Frontotemporal Dementia.
abstract: Frontotemporal dementia (FTD) is the second most common cause of dementia following Alzheimer's disease (AD). Between 20 and 50% of cases are familial. Mutations in MAPT, GRN and C9orf72 are found in 60% of familial FTD cases. C9orf72 mutations are the most common and account for 25%. Rarer mutations (<5%) occur in other genes such as VPC, CHMP2B, TARDP, FUS, ITM2B, TBK1 and TBP. The diagnosis is often challenging due to symptom overlap with AD and other conditions. We review the genetics, clinical presentations, neuroimaging, neuropathology, animal studies and therapeutic trials in FTD. We describe clinical scenarios including the original family with the tau stem loop mutation (+14) and also the recently discovered 'missing tau' mutation +15 that 'closed the loop' in 2015.
authors.affiliation: Department of Neurology, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Olszewska
authors.affiliation: Department of Neurology, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Roisin
authors.initials: R
authors.lastname: Lonergan
authors.affiliation: Department of Neurology, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Emer M
authors.initials: EM
authors.lastname: Fallon
authors.affiliation: Department of Neurology, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland. tlynch@dni.ie.
authors.forename: Tim
authors.initials: T
authors.lastname: Lynch
mesh_terms: D001921:Brain / Q000473:pathology; D000073885:C9orf72 Protein; D057180:Frontotemporal Dementia / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D009154:Mutation; D000077153:Progranulins; D011506:Proteins / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D011506:Proteins; D016875:tau Proteins
keywords: +15; DDPAC; FTDP-17; Frontotemporal dementia; Genetics