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.

Novel exon 1 progranulin gene variant in Alzheimer’s disease / F. Cortini, C. Fenoglio, I. Guidi, E. Venturelli, S. Pomati, A. Marcone, D. Scalabrini, C. Villa, F. Clerici, E. Dalla Valle, C. Mariani, S. Cappa, N. Bresolin, E. Scarpini, D. Galimberti. - In: EUROPEAN JOURNAL OF NEUROLOGY. - ISSN 1351-5101. - 15:10(2008 Oct), pp. 1111-1117. [10.1111/j.1468-1331.2008.02266.x]

Novel exon 1 progranulin gene variant in Alzheimer’s disease

F. Cortini;C. Fenoglio;I. Guidi;E. Venturelli;S. Pomati;D. Scalabrini;C. Villa;E. DALLA VALLE;C. Mariani;N. Bresolin;E. Scarpini;D. Galimberti
2008

Abstract

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.
allelic variant ; Alzheimer's disease ; frontotemporal lobar degeneration ; mutation ; polymorphism ; progranulin
Settore MED/26 - Neurologia
ott-2008
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/51933
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