GRN deletion in familial frontotemporal dementia showing association with clinical variability in 3 familial cases(208 visite) Milan G, Napoletano S, Pappata S, Gentile MT, Colucci-d'Amato L, Della Rocca G, Maciag A, Rossetti CP, Fucci L, Puca A, Grossi D, Postiglione A, Vitale E
Impact factor: 4.454, Impact factor a 5 anni: 5.06
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Parole chiave: Frontotemporal Dementia, Phenotype, Progranulin,
*** IBB - CNR *** Geriatric Clinic "Frullone" ASL Napoli 1, Naples, Italy., Institute of Protein Biochemistry (IBP), CNR, Naples, Italy., Institute of Bioimaging and Biostructures, CNR, Naples, Italy., Department of Environmental, Biological, Pharmaceutical Science and Technology, Second University of Naples, Caserta, Italy., Villa Camaldoli Foundation Clinic, Naples, Italy., IRCCS Multimedica, Milano, Italy., Department of Clinical Medicine & Surgery, University of Naples "Federico II", Naples, Italy., Department of Biology, University of Naples Federico II, Naples, Italy., IRCCS Multimedica, Milano, Italy; Department of Medicine, University of Salerno, Salerno, Italy., Villa Camaldoli Foundation Clinic, Naples, Italy; Department of Psychology, Second University of Naples, Caserta, Italy., Institute of Protein Biochemistry (IBP), CNR, Naples, Italy. Electronic address: email@example.com.,
Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritance patterns. We present evidence that all the available patients in these 3 familial cases are carrying the rare GRN gene exon 6 deletion g10325_10331delCTGCTGT (relative to nt 1 inNG_007886.1), alias Cys157LysfsX97. This mutation was previously described in 2 sporadic cases but was never associated with familial cases. Our patients demonstrate heterogeneous clinical phenotypes, such as the behavioral variant (bvFTD) in the affected men and the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) in the affected woman. Haploinsufficiency was revealed by both quantitative real-time PCR of the gene and protein analyses. These findings provide further support for a previously proposed role for the GRN gene in the genetic etiology of FTD and its phenotypic variability.
60 Records (54 escludendo Abstract e Conferenze). Impact factor totale: 296.229 (277.827 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 306.951 (282.197 escludendo Abstract e Conferenze).