A Novel Progranulin Mutation Causing Frontotemporal Lobar Degeneration with Heterogeneous Phenotypic Expression

作者：Rossi Giacomina^*; Piccoli Elena; Benussi Luisa; Caso Francesca; Redaelli Veronica; Magnani Giuseppe; Binetti Giuliano; Ghidoni Roberta; Perani Daniela; Giaccone Giorgio; Tagliavini Fabrizio

来源：Journal of Alzheimer's Disease, 2011, 23(1): 7-12.

DOI：10.3233/JAD-2010-101461

• Early onset
• frontotemporal lobar degeneration
• mutation
• plasma dosage
• progranulin

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by behavioural disturbances and cognitive decline. Here we describe an Italian family with FTLD showing remarkable phenotypic heterogeneity. Based on low plasma levels of progranulin, we analyzed the progranulin gene (GRN) in two patients with early onset and found the novel frame-shift mutation T278SfsX7. mRNA analysis confirmed the null effect of the mutation. The patients were homozygous for H1 MAPT haplotype, a disease modifier factor that can account for early age at onset. Being predictive for GRN null mutations, plasma progranulin dosage should be included in diagnostic work-up of dementia.

• 出版日期2011