Affiliations: [a] Division of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy | [b] NeuroBioGen Lab-Memory Clinic, IRCCS Centro S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy | [c] Department of Neurology, San Raffaele Scientific Institute, Milano, Italy | [d] Proteomics Unit, IRCCS Centro S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy | [e] Division of Neuroscience, Nuclear Medicine Department, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milano, Italy
Correspondence:
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Correspondence to: Giacomina Rossi, PhD, Division of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milano, Italy. Tel.: +39 02 2394 2260; Fax: +39 02 2394 2101; E-mail: grossi@istituto-besta.it.
Abstract: 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.
Keywords: Early onset, frontotemporal lobar degeneration, mutation, plasma dosage, progranulin
