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.
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.
Authors: Hideyuki Takahashi; Zoe A Klein; Sarah M Bhagat; Adam C Kaufman; Mikhail A Kostylev; Tsuneya Ikezu; Stephen M Strittmatter Journal: Acta Neuropathol Date: 2017-01-09 Impact factor: 17.088
Authors: Matthew Harms; Bruno A Benitez; Nigel Cairns; Breanna Cooper; Paul Cooper; Kevin Mayo; David Carrell; Kelley Faber; Jennifer Williamson; Tom Bird; Ramon Diaz-Arrastia; Tatiana M Foroud; Bradley F Boeve; Neill R Graff-Radford; Richard Mayeux; Sumitra Chakraverty; Alison M Goate; Carlos Cruchaga Journal: JAMA Neurol Date: 2013-06 Impact factor: 18.302
Authors: Gaurav Ghag; Lauren M Wolf; Randi G Reed; Nicholas P Van Der Munnik; Claudius Mundoma; Melissa A Moss; Vijayaraghavan Rangachari Journal: Protein Eng Des Sel Date: 2016-03-07 Impact factor: 1.650
Authors: Chiara Fenoglio; Daniela Galimberti; Francesca Cortini; John S K Kauwe; Carlos Cruchaga; Eliana Venturelli; Chiara Villa; Maria Serpente; Diego Scalabrini; Kevin Mayo; Laura M Piccio; Francesca Clerici; Diego Albani; Claudio Mariani; Gianluigi Forloni; Nereo Bresolin; Alison M Goate; Elio Scarpini Journal: J Alzheimers Dis Date: 2009 Impact factor: 4.472