Novel exon 1 progranulin gene variant in Alzheimer’s disease
F. Cortini
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Contributed equally to this work.
Search for more papers by this authorC. Fenoglio
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Contributed equally to this work.
Search for more papers by this authorI. Guidi
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorE. Venturelli
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorS. Pomati
Centre for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy
Search for more papers by this authorA. Marcone
Division of Neurology, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorD. Scalabrini
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorC. Villa
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorF. Clerici
Centre for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy
Search for more papers by this authorE. Dalla Valle
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorC. Mariani
Centre for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy
Search for more papers by this authorS. Cappa
Division of Neurology, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorN. Bresolin
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorE. Scarpini
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorD. Galimberti
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorF. Cortini
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Contributed equally to this work.
Search for more papers by this authorC. Fenoglio
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Contributed equally to this work.
Search for more papers by this authorI. Guidi
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorE. Venturelli
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorS. Pomati
Centre for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy
Search for more papers by this authorA. Marcone
Division of Neurology, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorD. Scalabrini
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorC. Villa
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorF. Clerici
Centre for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy
Search for more papers by this authorE. Dalla Valle
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorC. Mariani
Centre for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy
Search for more papers by this authorS. Cappa
Division of Neurology, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Search for more papers by this authorN. Bresolin
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorE. Scarpini
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorD. Galimberti
Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorAbstract
Background and purpose: Progranulin (PGRN) expression is increased in activated microglia in Alzheimer's disease (AD) brain, suggesting a potential role in this pathology.
Methods: A mutation scanning of exons and flanking regions of PGRN was carried out in 120 patients with sporadic frontotemporal lobar degeneration and 145 with sporadic AD.
Results: Amongst variants not yet deposited, a novel allelic variant was identified in Exon 1 (g100169G > A). It leads to an amino acidic change (p.Gly35Arg) and was observed in a patient with late onset AD. In silico analysis predicted that this mutation is possibly damaging. A second variant (g.100165C > T), resulting in a silent mutation (pAsp33Asp), was found in a patient with semantic dementia and in another with early onset AD. Both variants were absent in 226 controls. In addition, two rare non-pathogenic variants lying very close to PGRN splice-site regions (IVS2 + 7→G > A and IVS7 + 7→G > A) were observed. Transcriptional analysis in peripheral blood mononuclear cells from patients demonstrated they do not affect exon splicing.
Conclusions: A novel putative PGRN mutation leading to an amino acidic substitution was identified in a patient with clinical AD.
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