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Musollino G.,CNR Institute of Genetics and Biophysics Adriano Buzzati Traverso | Mastrolonardo G.,CNR Institute of Genetics and Biophysics Adriano Buzzati Traverso | Prezioso R.,CNR Institute of Genetics and Biophysics Adriano Buzzati Traverso | Pagano L.,AORN A. Cardarelli | And 3 more authors.
Annals of Hematology | Year: 2012

We report a new β-thalassaemia allele detected in a young Italian woman, suffering with mild nonhaemolytic anaemia (Hb<10 g/dL) and not showing Hb variant or Heinz bodies. The allele is characterised by duplication of tetranucleotide 'AG/CT' (+1344/+1347) including the invariant dinucleotide 'AG' of IVS-II acceptor splicing site and the first two nucleotides of codon 105. β-Globin complementary DNA (cDNA) sequencing did not reveal any mutation and qualitative analysis of the reverse transcription PCR reaction showed that only the proximal 3' splice site present in the duplicated gene is used giving race to an anomalous messenger RNA (mRNA) present in trace (1.5 %) because, most probably, rapidly degraded. In the anomalous mRNA, the insertion causes a frameshift and synthesis of an abnormal truncated β-chain (139 residues), unable to form Hb variant because of the severe conformational changes. The duplication might have arisen from secondary structures generated by quasi-palindromic sequence 5'-CCCA (C)AG/CT(CC)TGGG-3'. Restriction fragment length polymorphism analysis for the β-globin haplotype and familiar segregation analysis indicated that the mutant β-globin gene was associated with the haplotype V. © Springer-Verlag 2012. Source

Galbiati S.,San Raffaele Scientific Institute | Brisci A.,San Raffaele Scientific Institute | Damin F.,CNR Institute of Chemistry of Molecular Recognition | Gentilin B.,UO Dipartimentale di Genetica Medica | And 6 more authors.
Expert Opinion on Biological Therapy | Year: 2012

Introduction: In pregnancy, the discovery of fetal DNA in maternal blood outlined new scenarios for noninvasive prenatal diagnosis of numerous fetal pathological conditions based on a new source of fetal genetic material. Tests on fetal DNA circulating in maternal plasma are expected to replace or reduce invasive procedures, such as chorionic villi sampling and amniocentesis, that are typically carried out late in pregnancy and pose a risk of miscarriage. Areas covered: Nevertheless, at present, no accurate and simple methods for noninvasive prenatal diagnosis of genetic diseases are available, thus preventing a widespread clinical application. Expert opinion: Two highly different sensitive methodologies are reported both allowing the identification of fetal paternally inherited mutations in maternal plasma DNA during the first trimester of pregnancy in a clinically relevant genetic disease. The first one includes mutant enrichment amplification protocols either based on the use of PNA (peptide nucleic acids) or on CO-amplification at Lower Denaturation temperature-PCR (COLD-PCR). In the second approach, an extremely sensitive microarray substrates are exploited which allows the detection of fetal mutated alleles even without the need of any enrichment strategy. Beta-thalassemia has been chosen as a model of clinically relevant genetic disease. © 2012 Informa UK, Ltd. Source

Filippo P.D.,Electrophysiology and Pacing Unit | Ferrari P.,Electrophysiology and Pacing Unit | Iascone M.,Laboratorio Of Genetica Medica | Senni M.,Azienda Ospedaliera Papa Giovanni XXIII
Journal of Cardiovascular Electrophysiology | Year: 2015

A Tricky Case of Pediatric Overlap Syndrome We describe the case of 2-year-old baby with compound heterozygosity for paternal and maternal alleles mutation of α-subunit of the cardiac sodium channel (SCN5A), sinus node dysfunction, atrial flutter recurrences, and drug induced long-QT syndrome. In this setting, we chose at first to perform linear ablation of cavotricuspid isthmus resulting in a bidirectional isthmus block. As a second step, we decided to implant a miniaturized loop recorder that, with a minimally invasive procedure, permits us to follow the development of the disease in order to define the future strategy. After 8 months follow-up, automatic daily loop-recorder transmissions disclose the complete absence of any arrhythmia along with asymptomatic ventricular pauses due to sinus node dysfunction. Echocardiography shows normal findings, in particular no left ventricular dysfunction. © 2014 Wiley Periodicals, Inc. Source

Lalatta F.,UOSD di Genetica Medica | Folliero E.,UNITA di GENETICA CLINICA | Cavallari U.,Servizio di Genetica | Di Segni M.,Laboratorio Of Genetica Medica | And 6 more authors.
Italian Journal of Pediatrics | Year: 2012

Background: An increasing number of foetuses are recognized as having double Y because of the widespread use of prenatal screening using chorionic villus sampling and amniocentesis. 47, XYY karyotype occurs in about one out of 1,000 newborn males, but it is not often detected unless it is diagnosed during prenatal testing. Despite the fact that unbiased follow-up studies demonstrate largely normal post-natal development of young men with 47, XYY, there is a scarcity of controlled studies about the neurological, cognitive and behavioural phenotype which remains the main reason for anxiety and anticipatory negative attitudes of parents. Furthermore, prejudices still exist among professionals and the general population concerning the relationship between this sex chromosome aneuploidy and aggressive and antisocial behaviours. Methods. We report on the clinical follow-up of children diagnosed prenatally with a 47,XYY karyotype, whose parents received multidisciplinary counselling and support at time of diagnosis. The specific focus of our study is on auxology, facial features, developmental milestones, behaviour, detection of aggressiveness as well as the evaluation of parental attitudes toward prenatal counselling. Clinical evaluations including auxological measurements and dysmorphological descriptions were as conducted on 13 boys aged 9 month -7 years. The Child Behavior Check List test specific for age and a 15 item questionnaire were administered to both parents. An update of ongoing problems was carried out by means of a telephone interview two years later. Results: Our results show that, from birth, weight, height and head circumference were above average values while some facial features such mild hypertelorism are overrepresented when compared to parents' facial features. Language delay was detected in 8 out of 11 children older than 20 months. Parental attitudes were found to be favourable toward prenatal diagnoses of sexual chromosome aneuploidies. Conclusions: Our data, although limited, is similar to other observational studies, and serves to alert clinicians about opportunities to delineate new and appropriate educational interventions that target the specific learning challenges of XYY boys. Our experience better defines the early manifestation of XYY and should aid those involved in prenatal counselling and paediatric surveillance. © 2012 Lalatta et al.; licensee BioMed Central Ltd. Source

Morelli M.B.,University of Camerino | Offidani M.,Clinica di Ematologia | Alesiani F.,Unita di Oncoematologia | Discepoli G.,Laboratorio Of Genetica Medica | And 6 more authors.
International Journal of Cancer | Year: 2014

Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor. TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells. However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines. Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+). These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells. These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM. What's new Cannabidiol, a non-psychoactive component of Cannabis, has antitumor properties. This study investigated whether cannabidiol could assist another drug, bortezomib, in fighting multiple myeloma. Although patients respond well to bortezomib at first, most develop resistance to it over time. The authors looked in myeloma cell lines and patient samples for a protein, TRPV2, which interacts with cannabidiol. They found that cannabidiol, working alone or in concert with bortezomib, kills multiple myeloma cells, particularly when TRPV2 was expressed. These data suggest that treatment with cannabidiol may help sidestep the problem of patients developing resistance to bortezomib. © 2013 UICC. Source

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