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Causarano V.,Genomic Unit for the Diagnosis of Human Pathologies | Galbiati S.,Genomic Unit for the Diagnosis of Human Pathologies | Smid M.,San Raffaele Scientific Institute | Cremonesi L.,Genomic Unit for the Diagnosis of Human Pathologies | And 3 more authors.
Biochimica Clinica | Year: 2011

The study of cell-free RNA in maternal plasma provides a promising tool for monitoring some pregnancy pathologies, such as preeclampsia (PE). Due to the scarcity of RNA molecules in maternal plasma we introduced substantial improvements to the protocol previously described in the literature, including a preamplification step before quantitative analysis of target genes. By applying the improved protocol for plasma RNA quantification, we obtained an increase in sensitivity of about 10 quantification cycle values in detection of both the reference and target genes in a reliable amplification range. Among mRNA markers, the corticotropin-releasing hormone (CRH) transcript has been reported to be elevated in preeclamptic patients compared to women with uncomplicated pregnancy at the same gestational age. We applied the optimized protocol to the quantitative evaluation of CRH mRNA in women with overt PE, in a small cohort of women at risk of developing this pathology and in controls. Our preliminary results confirmed the increase of CRH mRNA concentration in preeclamptic women and showed that the transcript levels were significantly elevated in the last plasma sample collected from women at risk for the disease before the PE onset.

Di Resta C.,Vita-Salute San Raffaele University | Pietrelli A.,CNR Institute of Biomedical Technologies | Pietrelli A.,University of Milan | Sala S.,IRCCS San Raffaele Hospital | And 7 more authors.
Human Molecular Genetics | Year: 2015

Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder that can lead to sudden death, with a prevalence of 1:5000 in Caucasian population and affecting mainly male patients in their third to fourth decade of life. BrS is inherited as an autosomal dominant trait; however, to date genetic bases have been only partially understood. Indeed most mutations are located in the SCN5A gene, encoding the alpha-subunit of the Na+ cardiac channel, but >70% BrS patients still remain genetically undiagnosed. Although 21 other genes have been associated with BrS susceptibility, their pathogenic role is still unclear. A recent nextgeneration sequencing study investigated the contribution of 45 arrhythmia susceptibility genes in BrS pathogenesis, observing a significant enrichment only for SCN5A. In our study, we evaluated the distribution of putative functional variants in a wider panel of 158 genes previously associated with arrhythmic and cardiac defects in a cohort of 91 SCN5A-negative BrS patients. In addition, to identify genes significantly enriched in BrS, we performed a mutation burden test by using as control dataset European individuals selected from the 1000Genomes project. We confirmed BrS genetic heterogeneity and identified new potential BrS candidates such as DSG2 and MYH7, suggesting a possible genetic overlap between different cardiac disorders. © The Author 2015.

Rama P.,San Raffaele Scientific Institute | Knutsson K.A.,San Raffaele Scientific Institute | Rojo C.,San Raffaele Scientific Institute | Carrera P.,Genomic Unit for the Diagnosis of Human Pathologies | And 4 more authors.
Arquivos Brasileiros de Oftalmologia | Year: 2013

We report an atypical case of granular corneal dystrophy recurrence after deep anterior lamellar keratoplasty. We describe clinical features, histopathological analysis of the lamellar graft specimen and DNA analysis results. The slit-lamp examination and histopathological findings from the graft specimen indicated the confinement of the typical deposits of granular corneal dystrophy deep in the graft interface area. This localization is atypical, since in most cases recurrences in grafts tend to be initially superficial and situated in the epithelial or subepithelial corneal layers. Molecular genetic analysis revealed an already described mutation and a new intronic variant. The unusual localization and timing of this recurrence of granular corneal dystrophy after deep anterior lamellar keratoplasty suggests that corneal stromal keratocytes may play a role in the formation of granular deposits.

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