Extensive molecular analysis of patients bearing CFTR-related disorders.

Cystic fibrosis transmembrane conductance regulator (CFTR)–related disorders (CFTR-RDs) may present with pancreatic sufficiency, normal sweat test results, and better outcome. The detection rate of mutations is lower in CFTR-RD than in classic CF: mutations may be located in genes encoding proteins that interact with CFTR or support channel activity. We tested the whole CFTR coding regions in 99 CFTR-RD patients, looking for gene mutations in solute carrier (SLC) 26A and in epithelial Na channel (ENaC) in 33 patients who had unidentified mutations. CFTR analysis revealed 28 mutations, some of which are rare. Of these mutations, RT-PCR demonstrated that the novel 1525-1delG impairs exon 10 s…

Activity of mannose-binding lectin in centenarians

Summary We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general popula…

Precision Medicine in Oncology: Glossary of Relevant Scientific Terms

The conventional oncological approach was defined in the past as “one size fits all” and the tumors were treated according to the localization and the histopathological features. One of the future challenges in the field of oncology is the integration of translational research and technology innovation, in order to clarify unexplored aspects of the biology and the genetics of tumors, to develop a personalized treatment based on the molecular characteristics of the patient and his disease, that is the principle of precision medicine. New multidisciplinary teams are needed to ensure the integration of different professional profiles, including oncologists, pharmacologists, geneticians, and pa…

Prothrombotic gene variants as risk factors of acute myocardial infarction in young women

Abstract Background Acute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age. Methods We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy). Results In young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was signif…

Multicenter validation study for the certification of a CFTR gene scanning method using next generation sequencing technology.

AbstractBackground:Many European laboratories offer molecular genetic analysis of theCFTRgene using a wide range of methods to identify mutations causative of cystic fibrosis (CF) and CFTR-related disorders (CFTR-RDs). Next-generation sequencing (NGS) strategies are widely used in diagnostic practice, and CE marking is now required for most in vitro diagnostic (IVD) tests in Europe. The aim of this multicenter study, which involved three European laboratories specialized in CF molecular analysis, was to evaluate the performance of Multiplicom’s CFTR MASTR Dx kit to obtain CE-IVD certification.Methods:A total of 164 samples, previously analyzed with well-established “reference” methods for t…

Fetuin-A serum levels are not correlated to kidney function in long-lived subjects

Objectives: Serum Fetuin A has been identified as an inhibitor of ectopic calcification. It is reduced in subjects with chronic kidney disease (CKD) and it has been proposed as a potential link between CKD and the higher prevalence of arterial calcification observed in these patients. During ageing both the stiffening of arterial wall due to calcification and a decline in kidney function are frequent. The aim of the study is to investigate if Fetuin A serum levels are associated with ageing and with AHSG T256S polymorphism. Moreover, we aim at investigate whether serum Fetuin A is correlated to kidney function in this setting of senescence. Design and Methods: 256 health long-lived subjects…

Buerger`s Disease and Hyperhomocysteinemia: Is there a Relationship?

Thromboangiitis obliterans, also known as Buerger's disease, is a cause of juvenile lower limb ischaemia. Buerger's disease is idiopathic and one of diagnostic criteria is the absence of atherosclerotic risk factors other than smok- ing. A possible involvement of thrombophilia has been investigated and the role of hyperhomocysteinemia is still matter of discussion. We describe 9 patients with Buerger's disease followed-up for the past 3 years. We found a significant in- crease in circulating homocysteine levels (mean: 31.6 in patients vs 8.2 μmol/L in control subjects). We also analyzed the C677T mutation of MTHFR; 5/9 Buerger's patients were heterozygotes and 4/9 homozygotes for the mutati…

Activity of mannose-binding lectin in centenarians

We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population fro…

Molecular analysis of genes encoding CFTR interactors of SLC26 family in CF patients: preliminary results

MTHFR C677T allelic variant is not associated to plasma and cerebrospinal fluid homocysteine in amyotrophic lateral sclerosis

Amiotrophic lateral sclerosis (ALS) is a neurological disorder with a multifactorial etiopathogenesis including excitotoxicity, intracellular calcium increase and mitochondrial damage together with oxidative stress and apoptosis. Overall, the relationship between homocysteine (Hcy), motoneuron death and ALS appears to be complex and still under investigation. It has been already shown that Hcy is elevated in plasma and cerebrospinal fluid (CSF) of ALS patients, although mechanisms of hyperhomocysteinemia have not been elucidated yet. MTHFR C677T variant is the most common genetic determinant of increased homocysteinemia, but no studies regarding the effect of this polymorphism in ALS patien…