New PRSS1 and common CFTR mutations in a child with acute recurrent pancreatitis, could be considered an "Hereditary" form of pancreatitis ?

<p>Abstract</p> <p>Background</p> <p>acute recurrent pancreatitis is a complex multigenic disease, the diagnosis is even more difficult when this disease develops in a child.</p> <p>Case Presentation</p> <p>a 6-years old boy, hospitalized with epigastric pain radiating to the back showed high serum levels of serum amylase, lipase, CRP and erythrosedimentation rate. Several similar milder episodes of pain, followed by quick recovery and complete disappearance of symptoms were reported during the previous 13 months. The child was medically treated and after 7 days with normal clinic and laboratory tests was discharged with a hypolipidic diet. All the known aetiologic hypotheses were excluded by anamnestic investigation, clinical observation and biochemical evaluation, whereas, anatomic abnormality were excluded by a secretin stimulated magnetic resonance (MRI). At the last follow-up visit, (11 months later), the child showed a normal body weight and anthropometric profile, without further abdominal pain. Mutation screening for coding regions of <it>PRSS1, SPINK1, CFTR </it>and the new hereditary pancreatitis-associated chymotrypsin C (<it>CTRC</it>) genes showed a novel variation, c.541A > G (p.S181G), in the exon 4 of PRSS1 gene and the classical CF p.F508del mutation in the <it>CFTR. </it>Both mutations were present in his clinically normal mother and absent in the patient's father.</p> <p>Conclusions</p> <p>this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis. At the present knowledge it can be only stated that the combined genotype CFTR (F508del)/PRSS1 (S181G) is associated to a mild phenotype of acute recurrent pancreatitis in this child without any further conclusion on its pathogenetic role or prediction on the course of the disease.</p

Massive-Scale RNA-Seq Analysis of Non Ribosomal Transcriptome in Human Trisomy 21

Hybridization- and tag-based technologies have been successfully used in Down syndrome to identify genes involved in various aspects of the pathogenesis. However, these technologies suffer from several limits and drawbacks and, to date, information about rare, even though relevant, RNA species such as long and small non-coding RNAs, is completely missing. Indeed, none of published works has still described the whole transcriptional landscape of Down syndrome. Although the recent advances in high-throughput RNA sequencing have revealed the complexity of transcriptomes, most of them rely on polyA enrichment protocols, able to detect only a small fraction of total RNA content. On the opposite end, massive-scale RNA sequencing on rRNA-depleted samples allows the survey of the complete set of coding and non-coding RNA species, now emerging as novel contributors to pathogenic mechanisms. Hence, in this work we analysed for the first time the complete transcriptome of human trisomic endothelial progenitor cells to an unprecedented level of resolution and sensitivity by RNA-sequencing. Our analysis allowed us to detect differential expression of even low expressed genes crucial for the pathogenesis, to disclose novel regions of active transcription outside yet annotated loci, and to investigate a plethora of non-polyadenilated long as well as short non coding RNAs. Novel splice isoforms for a large subset of crucial genes, and novel extended untranslated regions for known genes—possibly novel miRNA targets or regulatory sites for gene transcription—were also identified in this study. Coupling the rRNA depletion of samples, followed by high-throughput RNA-sequencing, to the easy availability of these cells renders this approach very feasible for transcriptome studies, offering the possibility of investigating in-depth blood-related pathological features of Down syndrome, as well as other genetic disorders

Flow Optimization in Vascular Networks

The development of mathematical models for studying phenomena observed in vascular networks is very useful for its potential applications in medicine and physiology. Detailed 3D studies of flow in the arterial system based on the Navier-Stokes equations require high computational power, hence reduced models are often used, both for the constitutive laws and the spatial domain. In order to capture the major features of the phenomena under study, such as variations in arterial pressure and flow velocity, the resulting PDE models on networks require appropriate junction and boundary conditions. Instead of considering an entire network, we simulate portions of the latter and use inflow and outflow conditions which realistically mimic the behavior of the network that has not been included in the spatial domain. The resulting PDEs are solved numerically using a discontinuous Galerkin scheme for the spatial and Adam-Bashforth method for the temporal discretization. The aim is to study the e↵ect of truncation to the flow in the root edge of a fractal network, the e↵ect of adding or subtracting an edge to a given network, and optimal control strategies on a network in the event of a blockage or unblockage of an edge or of an entire subtree

Prevention of neural tube defects and maternal gestational diabetes through the inositol supplementation: preliminary results

Our study aims to demonstrate that the use in the preconceptional period until the 24th week of pregnancy of inositol and folic acid, first of all, preserves the product of conception from neural tube defects (NTDs) and then, thanks to inositol supplementation, it possibly counteracts and prevents the onset of maternal gestational diabetes (GDM)

The empowerment of translational research: lessons from laminopathies

The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy