title: A novel deletion in progranulin gene is associated with FTDP-17 and CBS.
abstract: In the last decade familial frontotemporal dementia (FFTD) has emerged as a distinct clinical disease entity characterized by clinical and genetic heterogeneity. Here, we provide an extensive clinical and genetic characterization of two Italian pedigrees presenting with FFTD (FAM047: 5 patients, 5 unaffected; FAM071: 4 patients, 11 unaffected). Genetic analysis showed a conclusive linkage (LOD score for D17S791/D17S951: 4.173) to chromosome 17 and defined a candidate region containing MAPT and PGRN genes. Recombination analysis assigned two different disease haplotypes to FAM047 and FAM071. In affected subjects belonging to both families, we identified a novel 4 bp deletion mutation in exon 7 of PGRN gene (Leu271LeufsX10) associated with a variable clinical presentation ranging from FTDP-17 to corticobasal syndrome. The age-related penetrance was gender dependent. Both mutations in MAPT and PGRN genes are associated with highly variable clinical phenotypes. Despite the profound differences in the biological functions of the encoded proteins, it is not possible to define a clinical phenotype distinguishing the disease caused by mutations in MAPT and PGRN genes.
authors.affiliation: NeuroBioGen Lab-Memory Clinic, IRCCS Centro San Giovanni di Dio-Fatebenefratelli, via Pilastroni 4, 25125 Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Elena
authors.initials: E
authors.lastname: Sina
authors.forename: Lara
authors.initials: L
authors.lastname: Gigola
authors.forename: Thomas
authors.initials: T
authors.lastname: Bettecken
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
mesh_terms: D000368:Aged; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D003704:Dementia / Q000000981:diagnostic imaging* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007558:Italy; D007930:Leucine / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D000077153:Progranulins; D017384:Sequence Deletion; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D007930:Leucine