Progranulin Genetic Screening in Frontotemporal Lobar Degeneration Patients From Central Italy

Abstract

Recently, mutations in the progranulin gene (GRN) were reported to account for the vast majority of Frontotemporal lobar Degeneration (FTLD) and a growing number of reports describe the implication of this gene in the development of the FTLD pathology with a significant variation in clinical features. To better clarify the contribution of GRN mutations to Italian FTLD, we screened 381 subjects: 171 cases and 210 healthy subjects, all from Central Italy, particularly of Tuscan origins. GRN gene was analyzed using High Resolution Melting Analysis and automated Genetic Analyzer. Human Progranulin ELISA Kit was employed to determine the plasma progranulin levels. The screening showed a total of six genetic variants in the GRN gene: 3 pathogenic and 3 non pathogenic in 13 out of 171 patients. The rare intronic variant IVS2 +7 G > A was found in one patient. The pathogenetic mutation, p.T272SfsX10, is confirmed as the most common GRN mutation in Italian FTLD patients with a frequency in our study of 2.32%. Moreover, we identified the first Italian patient with the p.R493X mutation, to date described in 43 families worldwide. Our data report, for the first time, the occurrence of GRN mutations in Tuscany, Central Italy, confirming that genetic variations in this gene could be a considerable genetic cause of FTLD and that genetic screening might be useful both in familial and sporadic FTLD patients.

Progranulin Is a Novel Independent Predictor of Disease Progression and Overall Survival in Chronic Lymphocytic Leukemia

“…In line with data from studies in normal individuals [25], [26] and patients with frontotemporal lobar degeneration [27], breast [17] and ovarian cancer [18], we found that Pgrn can be easily and reliably measured in the peripheral blood employing a commercially available enzyme-linked immunosorbent assay. Pairwise comparisons of fresh vs. thawed (data not shown) and plasma vs. serum samples collected from individual patients yielded remarkably similar results, suggesting that the assay used in our study was very robust.…”

Clinical and neuroimaging profiles to identify C9orf72‐FTD patients and serum Neurofilament to monitor the progression and the severity of the disease

“…Our cohort of C9orf72 patients presents a high variability in age at onset, duration of the disease, familial forms, and number of affected family members, in accordance with the genetic epidemiology of Italian patients with FTD …”

“…Our cohort of C9orf72 patients presents a high variability in age at onset, duration of the disease, familial forms, and number of affected family members, in accordance with the genetic epidemiology of Italian patients with FTD. [31][32][33][34][35][36] These features reflect the incomplete and age-related penetrance of the mutation, that determines the high phenotypic heterogeneity characteristic of this pathology. As expected, there are no statistically significant differences in incidence among males and females and in the distribution of APOE e4 allele.…”

Genetic Counseling and Testing for Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Italian Consensus Protocol

“…We developed a step-by-step algorithm for guiding genetic screening on the basis of biomarker results and clinical data, to reduce time and cost of the laboratory analysis. Specifically, the decision tree was defined according to (i) the observed frequency of genes in specific clinical phenotypes in the literature [49,[55][56][57][58], and specifically in Italian clinical series [52,[59][60][61][62][63][64][65], (ii) the direct experience of the Italian centres, and (iii) practical considerations, e.g. the high speed and low cost of a given screening procedure (i.e.…”