Graziella Mangone

Genetics Specialist

Name Graziella
Surname Mangone
Institution Institut du Cerveau et de la Moelle Epinière – Université Pierre et Marie Curie (Paris)
Address Centre d’Investigation Clinique Bâtiment ICM – 1ère étage – Aile A Hôpital Pitié-Salpêtrière 47 – 83 Boulevard de Hôpital 75013 Paris – France
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Graziella Mangone


  • Comparative analysis of rs12979860 SNP of the IFNL3 gene in children with hepatitis C and ethnic matched controls using 1000 Genomes Project data.

    Publication Date: 17/01/2014 on PloS one
    by Indolfi G, Mangone G, Bartolini E, Nebbia G, Calvo PL, Moriondo M, Tovo PA, de Martino M, Azzari C, Resti M
    DOI: 10.1371/journal.pone.0085899

    The rs12979860 single nucleotide polymorphism located on chromosome 19q13.13 near the interferon L3 gene (formerly and commonly known as interleukin 28B gene) has been associated in adults with both spontaneous and treatment induced clearance of hepatitis C virus. Although the exact mechanism of these associations remains unclear, it suggests that variation in genes involved in the immune response against the virus favours viral clearance. Limited and preliminary data are available on this issue in children. The aim of the present study was to evaluate, in a representative cohort of children with perinatal infection, the potential association between rs12979860 single nucleotide polymorphism and the outcome of hepatitis C virus infection. Alleles and genotypes frequencies were evaluated in 30 children who spontaneously cleared the virus and in 147 children with persistent infection and were compared with a population sample of ethnically matched controls with unknown hepatitis C status obtained using the 1000 Genomes Project data. The C allele and the C/C genotype showed greater frequencies in the clearance group (76.7% and 56.7%, respectively) when compared with both children with viral persistence (C allele 56.5%, p = 0.004; C/C genotype 32.7%, p = 0.02) and with the ethnically matched individuals (C allele 59.7%, p = 0.02; C/C genotype 34.7%, p = 0.03). Children with the C/C genotype were 2 times more likely to clear hepatitis C virus relative to children with the C/T and T/T genotypes combined (odds ratio: 2.7; 90% confidence intervals: 1.3-5.8). The present study provides the evidence that the rs12979860 single nucleotide polymorphism influences the natural history of hepatitis C virus in children.

  • Infiltrative treatment with Platelet Rich Plasma (PRP) in gonarthrosis.

    Publication Date: 01/01/2014 on Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases
    by Mangone G, Orioli A, Pinna A, Pasquetti P

    The aim of the study is to evaluate and to quantify the effects on the quality of life and the decrease of pain in short and middle term in patients affected of gonarthrosis and treated with a series of 3 injections of Platelet Rich Plasma (PRP). Gonarthrosis is one of the most frequent causes of disability on old ages and leads to difficulties in social, relational and daily activities (1). The most common therapeutic approach depends on the stage of the disease, it can be conservative (FKT), palliative (HA injections, chondro - protector) or reconstructive (TKR). Between October 2010 and January 2013, 72 patients referring to the outpatient clinic of the Rehabilitation Department of the Trauma Center, University Hospital of Careggi, Florence, have been enrolled if a primary gonarthrosis was diagnosed. The patients, after a hematology visit in Immune-Hematology Department of Careggi, have been evaluated with the WOMAC scale for the knee, VAS at rest and VAS in movement before a series of 3 injections with PRP (T0), after 1 months (T1), after 3 months (T2) after 6 year (T3) and after 1 year (T4) from the last injection. PRP injections can be considered a valid method in the control of pain, stiffness and joint function (24, 25) but it have to be considered as a second approach to the treatment of knee OA, due to the high cost and complexity of the procedure. Most of our patients shown good clinical results after one year, were satisfied of the treatment and returned to their previous daily activities.

  • Computer-assisted cognitive rehabilitation of attention deficits for multiple sclerosis: a randomized trial with fMRI correlates.

    Publication Date: 01/05/2013 on Neurorehabilitation and neural repair
    by Cerasa A, Gioia MC, Valentino P, Nisticò R, Chiriaco C, Pirritano D, Tomaiuolo F, Mangone G, Trotta M, Talarico T, Bilotti G, Quattrone A
    DOI: 10.1177/1545968312465194

    Although a growing body of evidence has highlighted the role of cognitive rehabilitation (CR) in the management of cognitive dysfunctions in multiple sclerosis (MS), there is still no evidence for a validated therapeutic approach.

  • Isolation and functional characterization of peptide agonists of PTPRJ, a tyrosine phosphatase receptor endowed with tumor suppressor activity.

    Publication Date: 19/10/2012 on ACS chemical biology
    by Paduano F, Ortuso F, Campiglia P, Raso C, Iaccino E, Gaspari M, Gaudio E, Mangone G, Carotenuto A, Bilotta A, Narciso D, Palmieri C, Agosti V, Artese A, Gomez-Monterrey I, Sala M, Cuda G, Iuliano R, Perrotti N, Scala G, Viglietto G, Alcaro S, Croce CM, Novellino E, Fusco A, Trapasso F
    DOI: 10.1021/cb300281t

    PTPRJ is a receptor-type protein tyrosine phosphatase whose expression is strongly reduced in the majority of investigated cancer cell lines and tumor specimens. PTPRJ negatively interferes with mitogenic signals originating from several oncogenic receptor tyrosine kinases, including HGFR, PDGFR, RET, and VEGFR-2. Here we report the isolation and characterization of peptides from a random peptide phage display library that bind and activate PTPRJ. These agonist peptides, which are able to both circularize and form dimers in acqueous solution, were assayed for their biochemical and biological activity on both human cancer cells and primary endothelial cells (HeLa and HUVEC, respectively). Our results demonstrate that binding of PTPRJ-interacting peptides to cell cultures dramatically reduces the extent of both MAPK phosphorylation and total phosphotyrosine levels; conversely, they induce a significant increase of the cell cycle inhibitor p27(Kip1). Moreover, PTPRJ agonist peptides both reduce proliferation and trigger apoptosis of treated cells. Our data indicate that peptide agonists of PTPRJ positively modulate the PTPRJ activity and may lead to novel targeted anticancer therapies.

  • Cerebellar-parietal dysfunctions in multiple sclerosis patients with cerebellar signs.

    Publication Date: 01/10/2012 on Experimental neurology
    by Cerasa A, Passamonti L, Valentino P, Nisticò R, Pirritano D, Gioia MC, Chiriaco C, Mangone G, Perrotta P, Quattrone A
    DOI: 10.1016/j.expneurol.2012.07.020

    Consistent findings have shown that the cerebellum is critically implicated in a broad range of cognitive processes including executive functions. Of note, cerebellar symptoms and a number of cognitive deficits have been widely reported in patients with multiple sclerosis (MS). This study investigated for the first time the role of cerebellar symptoms in modulating the neural networks associated with a cognitive task broadly used in MS patients (Paced Visual Serial Addition Test (PVSAT)). Twelve relapsing-remitting (RR) MS patients with prevalent cerebellar signs and symptoms (RR-MSc), 15 RR-MS patients without cerebellar manifestation (RR-MSnc) and 16 matched-healthy controls were examined during functional magnetic resonance imaging (fMRI). We tested whether the RR-MSc patients displayed abnormal activations within "cognitive" cerebellar regions and other areas typically engaged in working memory and tightly connected with the cerebellum. Despite similar behavioral performances during fMRI, RR-MSc patients displayed, relatively to both RR-MSnc patients and controls, significantly greater responses in the left cerebellar Crus I/Lobule VI. RR-MSc patients also displayed reduced functional connectivity between the left cerebellar Crus I and the right superior parietal lobule (FWE<.05). These results demonstrated that the presence of the cerebellar signs drastically impacts on the neurofunctional networks underlying working memory in MS. The altered communication between the cerebellum and a cortical area implicated in short-term buffering and storage of relevant information, offer new insights into the pathophysiological mechanisms of cognition in MS.

  • Serial T-SPOT.TB and quantiFERON-TB-Gold In-Tube assays to monitor response to antitubercular treatment in Italian children with active or latent tuberculosis infection.

    Publication Date: 01/09/2012 on The Pediatric infectious disease journal
    by Chiappini E, Bonsignori F, Mangone G, Galli L, Mazzantini R, Sollai S, Azzari C, de Martino M
    DOI: 10.1097/INF.0b013e31825d0d67

    We performed a prospective study to investigate T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-G-IT) dynamics during antitubercular treatment in active tuberculosis (TB) or latent TB. Eighteen children with latent TB and 26 with TB were enrolled. At 6 months of follow-up reversion rate was 5.88% (95% CI:0-13.79) for QFT-G-IT; 9.09% (95% CI:0.59-17.58) for T-SPOT.TB (P=0.921) in TB cases. Significant decline in quantitative response was observed exclusively in TB cases. Our results suggest that serial IGRA have limited use in children receiving antitubercular treatment.

  • Morbidity of teeth in the line of the fracture.

    Publication Date: 01/05/2011 on Minerva stomatologica
    by Mangone G, Longo F, Friscia M, Ferrara S, Califano L

    Management of a jaw fracture in which a tooth lies in the fracture line is controversial. In the past, teeth were generally removed because they were thought to be the cause of infections or locus minoris resistentiae. To provide a better indication in the management of teeth in the fracture line and the relate complications we retrospectively reviewed the files particularly in relation to treatment options.

  • Identification of a new mutation in the gene coding for hairless protein responsible for alopecia universalis: The importance of direct gene sequencing.

    Publication Date: 15/01/2011 on Dermatology online journal
    by Nucara S, Colao E, Mangone G, Baudi F, Fabiani F, Nocera D, Passafaro G, Longo T, Laria AE, Malatesta P, Amato R, Trapasso F, Perrotti N

    Mutations in the gene HR coding for the hairless protein are associated with atrichia with papular lesions (APL), an autosomal recessive form of alopecia universalis that is characterized by generalized scalp and body atrichia with papular lesions. We here describe a South Italian family of ancient Albanian heritage. The full phenotype with complete atrichia was expressed in 2 siblings, whereas the parents and one sister were unaffected. Direct sequencing of the gene coding for the hairless protein allowed the identification of a new mutation in exon 17. Consistent with the recessive inheritance of the disease, both the siblings were homozygous for the mutation, whereas the parents and the unaffected sister where heterozygous. A relevant discrepancy with a haplotype linkage study is reported, stressing the importance of gene sequencing in genetic diagnosis and counseling because linkage studies can be biased by recombination events.

  • Radial extracorporeal shock-wave therapy in rotator cuff calcific tendinosis.

    Publication Date: 01/05/2010 on Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases
    by Mangone G, Veliaj A, Postiglione M, Viliani T, Pasquetti P

    The objective of the study is to evaluate the effectiveness of Radial Extracorporeal Shock-wave Therapy (RESWT) compared with High Power LASER Therapy (HPLT) for the treatment of patients with Rotator Cuff Calcific Tendinosis (RCCT). RCCT is widely diffused, it is painful and invalidating. It is an important public health problem with social and economic implications. The most common therapeutic approach is a physiotherapic one. Both HPLT and RESWT give positive results. There is a debate on which is to be preferred. Therefore there is need to obtain scientific evidence to support either case. An observational study was carried out in the period between October 2008 and September 2009 in our outpatient clinic with 62 patients, divided into 3 groups: group A 36 patients treated only with RESWT, group B 26 patients treated only with HPLT and group C 16 patients with only short term improvement with HPLT retreated with RESWT. Patients were evaluated with Constant-Murley scale before and after treatment (immediately, 1 month and 3 months) for mean constant score, pain and range of movement. Data were examined statistically with SPSS. Criteria for inclusion and exclusion were defined. Patients treated with HPLT have shown good clinical results but have returned to original syndrome 1 month after treatment. RESWT has given improvement after treatment extended in time (3 months) in terms of pain and recover of functionality with a limited number of applications. The evidence collected indicates that RESWT is the method of choice.

  • Rehabilitation in peripheral non femoral fractures: a review.

    Publication Date: 01/01/2010 on Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases
    by Mangone G, Postiglione M, Pasquetti P

    This paper is a short review of the available information on peripheral non femoral fractures (PNFF) which are strictly related to osteoporosis. Particular attention is focused on wrist fractures in view of their frequent occurrence as indicated by world wide statistics. Of special interest is the definition of risk groups (old age), risk areas (developed countries) and risk factors. Reference is made to 2008 WHO guidelines for fracture risk assessment. PNFF are a serious concern to health authorities because their high incidence in constant growth, causes a serious burden on the health budget. The pathway of patient care is described, from initial evaluation (including bone fragility, multi-morbidity and risk factors) to specific diagnosis and treatment. The multiplicity of etiological factors involved requires multidisciplinary approach. This aspect justifies the importance given to rehabilitation, which is the longest part of patient care and is strictly connected to preventive measures. There is ample reference to falls, to exercises, to appropriate sports, to complications and to active and passive mobilization. The paper suggests research in areas related to PNFF, to health economics, epidemiology, prevention, health education, training and multidisciplinary coordination.