<?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%">Caorsi, Roberta</style></author><author><style face="normal" font="default" size="100%">Penco, Federica</style></author><author><style face="normal" font="default" size="100%">Grossi, Alice</style></author><author><style face="normal" font="default" size="100%">Insalaco, Antonella</style></author><author><style face="normal" font="default" size="100%">Omenetti, Alessia</style></author><author><style face="normal" font="default" size="100%">Alessio, Maria</style></author><author><style face="normal" font="default" size="100%">Conti, Giovanni</style></author><author><style face="normal" font="default" size="100%">Marchetti, Federico</style></author><author><style face="normal" font="default" size="100%">Picco, Paolo</style></author><author><style face="normal" font="default" size="100%">Tommasini, Alberto</style></author><author><style face="normal" font="default" size="100%">Martino, Silvana</style></author><author><style face="normal" font="default" size="100%">Malattia, Clara</style></author><author><style face="normal" font="default" size="100%">Gallizi, Romina</style></author><author><style face="normal" font="default" size="100%">Podda, Rosa Anna</style></author><author><style face="normal" font="default" size="100%">Salis, Annalisa</style></author><author><style face="normal" font="default" size="100%">Falcini, Fernanda</style></author><author><style face="normal" font="default" size="100%">Schena, Francesca</style></author><author><style face="normal" font="default" size="100%">Garbarino, Francesca</style></author><author><style face="normal" font="default" size="100%">Morreale, Alessia</style></author><author><style face="normal" font="default" size="100%">Pardeo, Manuela</style></author><author><style face="normal" font="default" size="100%">Ventrici, Claudia</style></author><author><style face="normal" font="default" size="100%">Passarelli, Chiara</style></author><author><style face="normal" font="default" size="100%">Zhou, Qing</style></author><author><style face="normal" font="default" size="100%">Severino, Mariasavina</style></author><author><style face="normal" font="default" size="100%">Gandolfo, Carlo</style></author><author><style face="normal" font="default" size="100%">Damonte, Gianluca</style></author><author><style face="normal" font="default" size="100%">Martini, Alberto</style></author><author><style face="normal" font="default" size="100%">Ravelli, Angelo</style></author><author><style face="normal" font="default" size="100%">Aksentijevich, Ivona</style></author><author><style face="normal" font="default" size="100%">Ceccherini, Isabella</style></author><author><style face="normal" font="default" size="100%">Gattorno, Marco</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study.</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><keywords><keyword><style  face="normal" font="default" size="100%">Adenosine Deaminase</style></keyword><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Age of Onset</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Mutational Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Heterozygote</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%">Immunoglobulins</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunosuppressive Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant</style></keyword><keyword><style  face="normal" font="default" size="100%">Intercellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Italy</style></keyword><keyword><style  face="normal" font="default" size="100%">Livedo Reticularis</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Polyarteritis Nodosa</style></keyword><keyword><style  face="normal" font="default" size="100%">Stroke</style></keyword><keyword><style  face="normal" font="default" size="100%">Thalidomide</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor Necrosis Factor-alpha</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">76</style></volume><pages><style face="normal" font="default" size="100%">1648-1656</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;OBJECTIVES: &lt;/b&gt;To analyse the prevalence of  mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Direct sequencing of  was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Biallelic homozygous or compound heterozygous  mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without  mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">10</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28522451?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%">Tanaka, Naoko</style></author><author><style face="normal" font="default" size="100%">Izawa, Kazushi</style></author><author><style face="normal" font="default" size="100%">Saito, Megumu K</style></author><author><style face="normal" font="default" size="100%">Sakuma, Mio</style></author><author><style face="normal" font="default" size="100%">Oshima, Koichi</style></author><author><style face="normal" font="default" size="100%">Ohara, Osamu</style></author><author><style face="normal" font="default" size="100%">Nishikomori, Ryuta</style></author><author><style face="normal" font="default" size="100%">Morimoto, Takeshi</style></author><author><style face="normal" font="default" size="100%">Kambe, Naotomo</style></author><author><style face="normal" font="default" size="100%">Goldbach-Mansky, Raphaela</style></author><author><style face="normal" font="default" size="100%">Aksentijevich, Ivona</style></author><author><style face="normal" font="default" size="100%">de Saint Basile, Geneviève</style></author><author><style face="normal" font="default" size="100%">Neven, Bénédicte</style></author><author><style face="normal" font="default" size="100%">van Gijn, Mariëlle</style></author><author><style face="normal" font="default" size="100%">Frenkel, Joost</style></author><author><style face="normal" font="default" size="100%">Aróstegui, Juan I</style></author><author><style face="normal" font="default" size="100%">Yagüe, Jordi</style></author><author><style face="normal" font="default" size="100%">Merino, Rosa</style></author><author><style face="normal" font="default" size="100%">Ibañez, Mercedes</style></author><author><style face="normal" font="default" size="100%">Pontillo, Alessandra</style></author><author><style face="normal" font="default" size="100%">Takada, Hidetoshi</style></author><author><style face="normal" font="default" size="100%">Imagawa, Tomoyuki</style></author><author><style face="normal" font="default" size="100%">Kawai, Tomoki</style></author><author><style face="normal" font="default" size="100%">Yasumi, Takahiro</style></author><author><style face="normal" font="default" size="100%">Nakahata, Tatsutoshi</style></author><author><style face="normal" font="default" size="100%">Heike, Toshio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study.</style></title><secondary-title><style face="normal" font="default" size="100%">Arthritis Rheum</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Arthritis Rheum.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Carrier Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Cryopyrin-Associated Periodic Syndromes</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Association Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mosaicism</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 Nov</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">63</style></volume><pages><style face="normal" font="default" size="100%">3625-32</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;OBJECTIVE: &lt;/b&gt;Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID), is a dominantly inherited systemic autoinflammatory disease. Although heterozygous germline gain-of-function NLRP3 mutations are a known cause of this disease, conventional genetic analyses fail to detect disease-causing mutations in ∼40% of patients. Since somatic NLRP3 mosaicism has been detected in several mutation-negative NOMID/CINCA syndrome patients, we undertook this study to determine the precise contribution of somatic NLRP3 mosaicism to the etiology of NOMID/CINCA syndrome.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;An international case-control study was performed to detect somatic NLRP3 mosaicism in NOMID/CINCA syndrome patients who had shown no mutation during conventional sequencing. Subcloning and sequencing of NLRP3 was performed in these mutation-negative NOMID/CINCA syndrome patients and their healthy relatives. Clinical features were analyzed to identify potential genotype-phenotype associations.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Somatic NLRP3 mosaicism was identified in 18 of the 26 patients (69.2%). Estimates of the level of mosaicism ranged from 4.2% to 35.8% (mean ± SD 12.1 ± 7.9%). Mosaicism was not detected in any of the 19 healthy relatives (18 of 26 patients versus 0 of 19 relatives; P &lt; 0.0001). In vitro functional assays indicated that the detected somatic NLRP3 mutations had disease-causing functional effects. No differences in NLRP3 mosaicism were detected between different cell lineages. Among nondescript clinical features, a lower incidence of mental retardation was noted in patients with somatic mosaicism. Genotype-matched comparison confirmed that patients with somatic NLRP3 mosaicism presented with milder neurologic symptoms.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;Somatic NLRP3 mutations were identified in 69.2% of patients with mutation-negative NOMID/CINCA syndrome. This indicates that somatic NLRP3 mosaicism is a major cause of NOMID/CINCA syndrome.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21702021?dopt=Abstract</style></custom1></record></records></xml>