Gianfranco Puoti

Researcher of Neurology

Name Gianfranco
Surname Puoti
Institution Università degli Studi della Campania Luigi Vanvitelli
Address II Division of Neurology & Center fo Rare Diseases Department of Medical Surgical, Neurological, Metabolic Sciences, and Aging, University of Campania Luigi Vanvitelli, Edificio 10 Via Sergio Pansini, 580131 Naples, Italy
Gianfranco Puoti


  • A mutation in the 5'-UTR of GRN gene associated with frontotemporal lobar degeneration: phenotypic variability and possible pathogenetic mechanisms.

    Publication Date: 01/01/2014 on Journal of Alzheimer's disease : JAD
    by Puoti G, Lerza MC, Ferretti MG, Bugiani O, Tagliavini F, Rossi G
    DOI: 10.3233/JAD-140717

    Frontotemporal lobar degeneration (FTLD) is a very heterogeneous disorder. It is genetically linked to three major genes: microtubule-associated protein tau (MAPT), progranulin (GRN), and C9ORF72. In particular, mutations in GRN account for 5-10% of all cases and give rise to a wide spectrum of clinical phenotypes, ranging from behavioral frontotemporal dementia (bvFTD) to primary progressive aphasia, including progressive non-fluent aphasia (PNFA) and semantic dementia, and corticobasal syndrome (CBS). We studied a family affected by FTLD whose members showed three different phenotypes: bvFTD, PNFA, and CBS. We performed plasma progranulin measurement before any genetic analyses and, due to the low level detected, we sequenced GRN and found the new mutation EX0-5' splice site A > G in the 5'-UTR region, where no pathogenic mutations had been previously demonstrated. Genetic analyses of MAPT and C9ORF72 were normal. GRN mRNA expression showed about 50% reduction caused by this mutation, and similar results were found for progranulin level. Testing of nonsense mediated RNA decay gave negative results, suggesting a different mechanism of mRNA degradation. In summary, the EX0-5' splice site A > G mutation widens the GRN regions affected by null mutations, including the 5'-UTR, and confirms once more the large phenotypic variability linked to GRN mutations.

  • New-onset refractory status epilepticus mimicking herpes virus encephalitis.

    Publication Date: 19/09/2013 on Case reports in neurology
    by Puoti G, Elefante A, Saracino D, Capasso A, Cotrufo R, Anello CB
    DOI: 10.1159/000355273

    New-onset refractory status epilepticus (NORSE) is a recently defined clinical entity that describes patients who present with status epilepticus of unclear etiology that is highly refractory to therapy. Magnetic resonance imaging (MRI) of NORSE usually discloses no specific abnormalities except for an occasional mild T2/FLAIR hyperintense signal of the mesial temporal lobe. Here, we report a peculiar case of NORSE in which brain MRI showed massive alteration of both temporal lobes, with features strongly supporting the diagnosis of herpes virus encephalitis, but lacking any laboratory evidence of viral infection in the blood and cerebrospinal fluid. It showed also striking signal alterations in the thalamus, which got worse in the course of the disease. This report emphasizes the possibility that seizure activity alone plays a critical role in both determining the disease and whether it will be self-sustaining.

  • Protease-sensitive prions with 144-bp insertion mutations.

    Publication Date: 01/03/2013 on Aging
    by Xiao X, Cali I, Dong Z, Puoti G, Yuan J, Qing L, Wang H, Kong Q, Gambetti P, Zou WQ
    DOI: 10.18632/aging.100543

    Insertion of 144-base pair (bp) containing six extra octapeptide repeats between residues 51 and 91 of prion protein (PrP) gene is associated with inherited prion diseases. Most cases linked to this insertion examined by Western blotting showed detectable proteinase K-resistant PrPSc (rPrPSc) resembling PrPSc type 1 and type 2 in sporadic Creutzfeldt-Jakob disease (sCJD), or PrP7-8 in Gerstmann-Sträussler-Scheinker disease. However, cases lacking detectable rPrPSc also have been reported. Which PrP conformer is associated with neuropathological changes in the cases without detectable rPrPSc remains to be determined. Here we report that while all six but one subjects with the 144-bp insertion mutations examined display the pathognomonic PrP patches in the cerebellum, one of them exhibits no detectable typical rPrPSc even in PrPSc-enriched preparations. Instead, a large amount of abnormal PrP is captured from this case by gene 5 protein and sodium phosphotungstate, reagents that have been proved to specifically capture abnormal PrP. All captured abnormal PrP from the cerebellum and other brain regions is virtually sensitive to PK-digestion (termed sPrPSc). The presence of the predominant sPrPSc but absence of rPrPSc in this 144-bp insertion-linked inherited CJD case suggests that mutant sPrPSc is the main component of the PrP deposit patches and sPrPSc is sufficient to cause neurotoxicity and prion disease.

  • Non-alcoholic acute Wernicke's encephalopathy: role of MRI in non typical cases.

    Publication Date: 01/12/2012 on European journal of radiology
    by Elefante A, Puoti G, Senese R, Coppola C, Russo C, Tortora F, de Divitiis O, Brunetti A
    DOI: 10.1016/j.ejrad.2012.08.006

    Acute Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency, most commonly found in chronic alcoholics. It is not so easy to suspect acute WE when the clinical picture does not include all the typical symptoms and alcohol abuse is not reported. Three rare cases of Wernicke's encephalopathy (WE) in non-alcoholic patients are reported.

  • A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease.

    Publication Date: 07/08/2012 on Neurology
    by Hamlin C, Puoti G, Berri S, Sting E, Harris C, Cohen M, Spear C, Bizzi A, Debanne SM, Rowland DY
    DOI: 10.1212/WNL.0b013e318263565f

    To compare the respective efficiency of CSF tau (quantitative) and CSF 14-3-3 protein (qualitative) in the diagnosis of prion disease.

  • Sporadic human prion diseases: molecular insights and diagnosis.

    Publication Date: 01/07/2012 on The Lancet. Neurology
    by Puoti G, Bizzi A, Forloni G, Safar JG, Tagliavini F, Gambetti P
    DOI: 10.1016/S1474-4422(12)70063-7

    Human prion diseases can be sporadic, inherited, or acquired by infection. Distinct clinical and pathological characteristics separate sporadic diseases into three phenotypes: Creutzfeldt-Jakob disease (CJD), fatal insomnia, and variably protease-sensitive prionopathy. CJD accounts for more than 90% of all cases of sporadic prion disease; it is commonly categorised into five subtypes that can be distinguished according to leading clinical signs, histological lesions, and molecular traits of the pathogenic prion protein. Three subtypes affect prominently cognitive functions whereas the other two impair cerebellar motor activities. An accurate and timely diagnosis depends on careful clinical examination and early performance and interpretation of diagnostic tests, including electroencephalography, quantitative assessment of the surrogate markers 14-3-3, tau, and of the prion protein in the CSF, and neuroimaging. The reliability of CSF tests is improved when these tests are interpreted alongside neuroimaging data.

  • Variably protease-sensitive prionopathy: a novel disease of the prion protein.

    Publication Date: 01/11/2011 on Journal of molecular neuroscience : MN
    by Gambetti P, Puoti G, Zou WQ
    DOI: 10.1007/s12031-011-9543-1

    Variably protease-sensitive prionopathy (VPSPr) is a novel disease involving the prion protein (PrP) that has clinical similarities with non-Alzheimer's dementias especially frontotemporal dementia, diffuse Lewis body disease, and normal pressure hydrocephalus. VPSPr can be distinguished from sporadic Creutzfeldt-Jakob disease (sCJD) especially for the characteristics of the abnormal PrP. Furthermore, although VPSPr like sCJD affects patients with the three PrP genotypes as determined by the common methionine/valine polymorphism, the allelic prevalence is very different in the two diseases. These findings suggest that VPSPr is basically different from classical prion diseases such as sCJD being perhaps more akin to other neurodegenerative dementias.

  • Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP.

    Publication Date: 01/08/2010 on Archives of neurology
    by Bugiani O, Giaccone G, Rossi G, Mangieri M, Capobianco R, Morbin M, Mazzoleni G, Cupidi C, Marcon G, Giovagnoli A, Bizzi A, Di Fede G, Puoti G, Carella F, Salmaggi A, Romorini A, Patruno GM, Magoni M, Padovani A, Tagliavini F
    DOI: 10.1001/archneurol.2010.178

    To report the clinical, genetic, neuroimaging, and neuropathologic studies of patients with the hereditary cerebral hemorrhage with amyloidosis linked to the APP E693K mutation.

  • Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein.

    Publication Date: 01/08/2010 on Annals of neurology
    by Zou WQ, Puoti G, Xiao X, Yuan J, Qing L, Cali I, Shimoji M, Langeveld JP, Castellani R, Notari S, Crain B, Schmidt RE, Geschwind M, Dearmond SJ, Cairns NJ, Dickson D, Honig L, Torres JM, Mastrianni J, Capellari S, Giaccone G, Belay ED, Schonberger LB, Cohen M, Perry G, Kong Q, Parchi P, Tagliavini F, Gambetti P
    DOI: 10.1002/ana.22094

    The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV).

  • A novel insertional mutation in the prion protein gene: clinical and bio-molecular findings.

    Publication Date: 01/12/2008 on Journal of neurology, neurosurgery, and psychiatry
    by Mauro C, Giaccone G, Piscosquito G, Lavorgna A, Nigro M, Di Fede G, Leonardi A, Coppola C, Formisano S, Tagliavini F, Cotrufo R, Puoti G
    DOI: 10.1136/jnnp.2007.142976

    A young man, presenting with early onset of personality and behavioural changes followed by slowly progressive cognitive impairment associated with marked bi-parietal cerebral atrophy, was found to carry a novel seven extra-repeat insertional mutation in the prion protein gene (PRNP). In vitro, the mutated recombinant prion protein (PrP) showed biochemical properties that were consistent with pathological PrP variants. Our results further underline the heterogeneity of neurological pictures associated with insertional mutations of PRNP, indicating the diagnostic difficulties of sporadic cases with early-onset atypical dementia.