BACKGROUND: Frontotemporal dementia is a clinically and genetically heterogeneous syndrome. Mutations in two genes, Microtubule Associated Protein Tau (MAPT) and Progranulin (PGRN), and rarely Presenilin mutations, have been causally linked to this disorder. OBJECTIVE: To investigate the presence of PGRN, PSEN1, PSEN2 and APP mutations in a group of familial early-onset frontotemporal dementia (f-EOFTD) patients negative for MAPT gene mutations. SUBJECTS AND METHODS: We prospectively studied 17 unrelated subjects diagnosed with f-EOFTD (one case neuropathologically confirmed as FTD-Ub+). Among these subjects eight belonged to eight autosomal dominant families unrelated to each other, and nine had at least one first degree relative affected by dementia. RESULTS: We identified two novel heterozygous mutations in two unrelated patients, Cys139Arg in the PGRN gene and Val412Ile in the PSEN1 gene. CONCLUSIONS: Early-onset f-FTD remains a heterogeneous disorder from a genetic point of view. PGRN mutation frequency was low in our sample. The presence of a novel PSEN1 mutation suggests that presenilin molecular studies should be performed when screening for MAPT and PGRN genes is negative.
BACKGROUND: Frontotemporal dementia is a clinically and genetically heterogeneous syndrome. Mutations in two genes, Microtubule Associated Protein Tau (MAPT) and Progranulin (PGRN), and rarely Presenilin mutations, have been causally linked to this disorder. OBJECTIVE: To investigate the presence of PGRN, PSEN1, PSEN2 and APP mutations in a group of familial early-onset frontotemporal dementia (f-EOFTD) patients negative for MAPT gene mutations. SUBJECTS AND METHODS: We prospectively studied 17 unrelated subjects diagnosed with f-EOFTD (one case neuropathologically confirmed as FTD-Ub+). Among these subjects eight belonged to eight autosomal dominant families unrelated to each other, and nine had at least one first degree relative affected by dementia. RESULTS: We identified two novel heterozygous mutations in two unrelated patients, Cys139Arg in the PGRN gene and Val412Ile in the PSEN1 gene. CONCLUSIONS: Early-onset f-FTD remains a heterogeneous disorder from a genetic point of view. PGRN mutation frequency was low in our sample. The presence of a novel PSEN1 mutation suggests that presenilin molecular studies should be performed when screening for MAPT and PGRN genes is negative.
Authors: Jun Wang; Philip Van Damme; Carlos Cruchaga; Michael A Gitcho; Jose Manuel Vidal; Manuel Seijo-Martínez; Lei Wang; Jane Y Wu; Wim Robberecht; Alison Goate Journal: J Neurochem Date: 2009-12-17 Impact factor: 5.372
Authors: Eliana Marisa Ramos; Deepika Reddy Dokuru; Victoria Van Berlo; Kevin Wojta; Qing Wang; Alden Y Huang; Sandeep Deverasetty; Yue Qin; Marka van Blitterswijk; Jazmyne Jackson; Brian Appleby; Yvette Bordelon; Patrick Brannelly; Danielle E Brushaber; Bradford Dickerson; Susan Dickinson; Kimiko Domoto-Reilly; Kelley Faber; Julie Fields; Jamie Fong; Tatiana Foroud; Leah K Forsberg; Ralitza Gavrilova; Nupur Ghoshal; Jill Goldman; Jonathan Graff-Radford; Neill Graff-Radford; Ian Grant; Murray Grossman; Hilary W Heuer; Ging-Yuek R Hsiung; Edward Huey; David Irwin; Kejal Kantarci; Anna Karydas; Daniel Kaufer; Diana Kerwin; David Knopman; John Kornak; Joel H Kramer; Walter Kremers; Walter Kukull; Irene Litvan; Peter Ljubenkov; Codrin Lungu; Ian Mackenzie; Mario F Mendez; Bruce L Miller; Chiadi Onyike; Alexander Pantelyat; Rodney Pearlman; Len Petrucelli; Madeline Potter; Katherine P Rankin; Katya Rascovsky; Erik D Roberson; Emily Rogalski; Leslie Shaw; Jeremy Syrjanen; Maria Carmela Tartaglia; Nadine Tatton; Joanne Taylor; Arthur Toga; John Q Trojanowski; Sandra Weintraub; Bonnie Wong; Zbigniew Wszolek; Rosa Rademakers; Brad F Boeve; Howard J Rosen; Adam L Boxer; Giovanni Coppola Journal: Alzheimers Dement Date: 2020-01 Impact factor: 21.566
Authors: Eliana Marisa Ramos; Christos Koros; Deepika Reddy Dokuru; Victoria Van Berlo; Christos Kroupis; Kevin Wojta; Qing Wang; Nikolaos Andronas; Stavroula Matsi; Ion N Beratis; Alden Y Huang; Suzee E Lee; Anastasios Bonakis; Chryseis Florou-Hatziyiannidou; Stella Fragkiadaki; Dionysia Kontaxopoulou; Dimitrios Agiomyrgiannakis; Vasiliki Kamtsadeli; Niki Tsinia; Vasiliki Papastefanopoulou; Maria Stamelou; Bruce L Miller; Leonidas Stefanis; John D Papatriantafyllou; Sokratis G Papageorgiou; Giovanni Coppola Journal: Neurobiol Aging Date: 2018-11-03 Impact factor: 4.673
Authors: NiCole Finch; Matt Baker; Richard Crook; Katie Swanson; Karen Kuntz; Rebecca Surtees; Gina Bisceglio; Anne Rovelet-Lecrux; Bradley Boeve; Ronald C Petersen; Dennis W Dickson; Steven G Younkin; Vincent Deramecourt; Julia Crook; Neill R Graff-Radford; Rosa Rademakers Journal: Brain Date: 2009-01-21 Impact factor: 13.501