<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Rusmini, Marta</style></author><author><style face="normal" font="default" size="100%">Federici, Silvia</style></author><author><style face="normal" font="default" size="100%">Caroli, Francesco</style></author><author><style face="normal" font="default" size="100%">Grossi, Alice</style></author><author><style face="normal" font="default" size="100%">Baldi, Maurizia</style></author><author><style face="normal" font="default" size="100%">Obici, Laura</style></author><author><style face="normal" font="default" size="100%">Insalaco, Antonella</style></author><author><style face="normal" font="default" size="100%">Tommasini, Alberto</style></author><author><style face="normal" font="default" size="100%">Caorsi, Roberta</style></author><author><style face="normal" font="default" size="100%">Gallo, Eleonora</style></author><author><style face="normal" font="default" size="100%">Olivieri, Alma Nunzia</style></author><author><style face="normal" font="default" size="100%">Marzano, AngeloValerio</style></author><author><style face="normal" font="default" size="100%">Coviello, Domenico</style></author><author><style face="normal" font="default" size="100%">Ravazzolo, Roberto</style></author><author><style face="normal" font="default" size="100%">Martini, Alberto</style></author><author><style face="normal" font="default" size="100%">Gattorno, Marco</style></author><author><style face="normal" font="default" size="100%">Ceccherini, Isabella</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases.</style></title><secondary-title><style face="normal" font="default" size="100%">Ann Rheum Dis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Ann. Rheum. Dis.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015 Sep 17</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">ENG</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;OBJECTIVES: &lt;/b&gt;Systemic auto-inflammatory disorders (SAIDs) are a heterogeneous group of monogenic diseases sharing a primary dysfunction of the innate immune system. More than 50% of patients with SAID does not show any mutation at gene(s) tested because of lack of precise clinical classification criteria and/or incomplete gene screening. To improve the molecular diagnosis and genotype interpretation of SAIDs, we undertook the development of a next-generation sequencing (NGS)-based protocol designed to simultaneous screening of 10 genes.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Fifty patients with SAID, already genotyped for the respective causative gene(s), were massively sequenced for the coding portions of MEFV, MVK, TNFRSF1A, NLRP3, NLRP12, NOD2, PSTPIP1, IL1RN, LPIN2 and PSMB8. Three different bioinformatic pipelines (Ion Reporter, CLC Bio Genomics Workbench, GATK-based in-house workflow) were compared.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Once resulting variants were compared with the expected mutation list, no workflow turned out to be able to detect all the 79 variants known in the 50 DNAs. Additional variants were also detected, validated by Sanger sequencing and compared to assess true and false positive detection rates of the three workflows. Finally, the overall clinical picture of 34 patients was re-evaluated in the light of the new mutations found.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;The present gene panel has resulted suitable for molecular diagnosis of SAIDs. Moreover, genotype-phenotype correlation has confirmed that the interpretation of NGS data in patients with an undefined inflammatory phenotype is remarkably difficult, thus supporting the need of evidence-based and validated clinical criteria to be used concurrently with the genetic analysis for the final diagnosis and classification of patients with SAIDs.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26386126?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Crovella, Sergio</style></author><author><style face="normal" font="default" size="100%">Segat, Ludovica</style></author><author><style face="normal" font="default" size="100%">Amato, Annalisa</style></author><author><style face="normal" font="default" size="100%">Athanasakis, Emmanouil</style></author><author><style face="normal" font="default" size="100%">Bezzerri, Valentino</style></author><author><style face="normal" font="default" size="100%">Braggion, Cesare</style></author><author><style face="normal" font="default" size="100%">Casciaro, Rosaria</style></author><author><style face="normal" font="default" size="100%">Castaldo, Giuseppe</style></author><author><style face="normal" font="default" size="100%">Colombo, Carla</style></author><author><style face="normal" font="default" size="100%">Covone, Angela Elvira</style></author><author><style face="normal" font="default" size="100%">De Rose, Virginia</style></author><author><style face="normal" font="default" size="100%">Gagliardini, Rolando</style></author><author><style face="normal" font="default" size="100%">Lanzara, Carmen</style></author><author><style face="normal" font="default" size="100%">Minicucci, Laura</style></author><author><style face="normal" font="default" size="100%">Morgutti, Marcello</style></author><author><style face="normal" font="default" size="100%">Nicolis, Elena</style></author><author><style face="normal" font="default" size="100%">Pardo, Francesca</style></author><author><style face="normal" font="default" size="100%">Quattrucci, Serena</style></author><author><style face="normal" font="default" size="100%">Raia, Valeria</style></author><author><style face="normal" font="default" size="100%">Ravazzolo, Roberto</style></author><author><style face="normal" font="default" size="100%">Seia, Manuela</style></author><author><style face="normal" font="default" size="100%">Stanzial, Valentino</style></author><author><style face="normal" font="default" size="100%">Termini, Lisa</style></author><author><style face="normal" font="default" size="100%">Zazzeron, Laura</style></author><author><style face="normal" font="default" size="100%">Cabrini, Giulio</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients.</style></title><secondary-title><style face="normal" font="default" size="100%">Clin Chem Lab Med</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Clin. Chem. Lab. Med.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">5' Untranslated Regions</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">beta-Defensins</style></keyword><keyword><style  face="normal" font="default" size="100%">Cystic Fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cystic Fibrosis Transmembrane Conductance Regulator</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Homozygote</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Italy</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">49</style></volume><pages><style face="normal" font="default" size="100%">49-54</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G&gt;A, c.-44C&gt;G and c.-20G&gt;A) in the 5' untranslated region (5' UTR) of the β defensin 1 (DEFB1) gene and the CF pulmonary phenotype.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan(®) allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42).&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;For the c.-20G&gt;A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.-20G&gt;A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21077791?dopt=Abstract</style></custom1></record></records></xml>