Epidemiology and genetics of frontotemporal dementia: a door-to-door survey in Southern Italy

Bernardi, Livia; Frangipane, Francesca; Smirne, Nicoletta; Colao, Rosanna; Puccio, Gianfranco; Curcio, Sabrina A.M.; Mirabelli, Maria; Maletta, Raffaele; Anfossi, Maria; Gallo, Maura; Geracitano, Silvana; Conidi, Maria Elena; Lorenzo, Raffale Di; Clodomiro, Alessandra; Cupidi, Chiara; Marzano, Sandra; Comito, Francesco; Valenti, Vincenzo; Zirilli, Maria Angela; Ghani, Mahdi; Xi, Zhengrui; Sato, Christine; Moreno, Danielle; Borelli, Annelisa; Leone, Rosa; George-Hyslop, Peter St; Rogaeva, Ekaterina; Bruni, Amalia C.

doi:10.1016/j.neurobiolaging.2012.06.017

Cited by 47 publications

(53 citation statements)

References 29 publications

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“…Some missense GRN mutations produce normal PGRN plasma levels (A324T, R433W, P34S, P451L and C521Y; Sleegers et al, 2009; Finch et al, 2009; Almeida et al, 2014; Wang et al, 2010), while other missense GRN mutations produce intermediate PGRN plasma levels, between values typical of normal and null GRN mutations (C139R, R432C, R564C, C126W and A266P; Finch et al, 2009; Sleegers et al, 2009; Bernardi et al, 2012). Only the clearly pathogenic A9D mutation produces plasma PGRN levels typical of null GRN mutations (Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Missense mutations in progranulin gene associated with frontotemporal lobar degeneration: study of pathogenetic features

Karch

Ezerskiy

Redaelli

et al. 2016

Neurobiology of Aging

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GRN, the gene coding for the progranulin (PGRN), was recognized as a gene linked to frontotemporal lobar degeneration (FTLD). The first mutations identified were null mutations giving rise to haploinsufficiency. Missense mutations were subsequently detected but only a small subset has been functionally investigated. We identified missense mutations (C105Y, A199V and R298H) in FTLD cases with family history and/or with low plasma PGRN levels. The aim of this study was to determine their pathogenicity. We performed functional studies, analyzing PGRN expression, secretion and cleavage by elastase. GRN C105Y affected both secretion and elastase cleavage, likely representing a pathogenic mutation. GRN A199V did not alter the physiological properties of PGRN and GRN R298H produced only moderate effects on PGRN secretion, indicating that their pathogenicity is uncertain. In the absence of strong segregation data and neuropathological examinations, genetic, biomarker, and functional studies can be applied to an algorithm to assess the likelihood of pathogenicity for a mutation. This information can improve our understanding of the complex mechanisms by which GRN mutations lead to FTLD.

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Section: Introductionmentioning

confidence: 99%

Missense mutations in progranulin gene associated with frontotemporal lobar degeneration: study of pathogenetic features

Karch

Ezerskiy

Redaelli

et al. 2016

Neurobiology of Aging

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“…Only in 2006 the discovery of PGRN gene allowed to identify the causative gene in the Biv pedigree 16 . After ten years, a door-to-door population study in the same village showed an unusual higher incidence of FTD compared to AD and a high prevalence of GRN mutations, confirming the genetic peculiarity of this geographical area 17 .…”

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confidence: 61%

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2017

J Neurol Neuromedicine

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“…Regarding the sex distribution of FTD, there is a disagreement, as to whether there is a male predominance [22][23][24][25][26][27]. FTD is further subclassified by symptoms and presentation into two main categories: behavioral variant (bvFTD) and the language variant primary progressive aphasia (PPA) which is further divided into semantic dementia (SD) and progressive nonfluent aphasia (PNFA).…”

Section: Clinical Description Of Ftd and Alsmentioning

confidence: 99%

Cognitive Profile of C9orf72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Patel

Sampson

2015

Curr Neurol Neurosci Rep

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This review article focuses on the cognitive profile associated with the C9orf72 gene with GGGGCC (G4C2) hexanucleotide repeat expansions that is commonly found in both familial and sporadic forms of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in order to aid clinicians in the screening process. In this growing clinical continuum between FTD and ALS, understanding and recognizing a neurocognitive profile is important for diagnosis. Key features of this profile include executive dysfunction with memory impairment and language deficits as the disease progresses. Behaviorally, patients are prone to disinhibition, apathy, and psychosis. With the discovery of this mutation, studies have begun to characterize the different phenotypes associated with this mutation in terms of epidemiology, clinical presentation, imaging, and pathology. Greater awareness and increased surveillance for this mutation will benefit patients and their families in terms of access to genetic counseling, research studies, and improved understanding of the disease process.

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Epidemiology and genetics of frontotemporal dementia: a door-to-door survey in Southern Italy

Cited by 47 publications

References 29 publications

Missense mutations in progranulin gene associated with frontotemporal lobar degeneration: study of pathogenetic features

Missense mutations in progranulin gene associated with frontotemporal lobar degeneration: study of pathogenetic features

Untitled

Cognitive Profile of C9orf72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

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