Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

A European survey of perendoscopic treatment of biliary complications in patients with alveolar echinococcosis.

Biliary complications represent a turning point in the course of Alveolar Echinococcosis (AE). We conducted a European survey to collect data on the current usage and results of perendoscopic interventions (PEIs) for their treatment. Patient's characteristics and follow-up until January 31st, 2015 were recorded using an online questionnaire. From 18 centers 129 PEIs were analyzed in 38 patients; 139 plastic stents were inserted during 85 PEIs; median time between stent placements was significantly longer when 3 stents or more were placed. Initial symptoms disappeared in 95% and long-term bile duct patency was obtained in 73% of cases. Cholangitis was a more frequent complication of the PEIs (10%) than in other indications; intensive lavage of the bile ducts may prevent this complication. European centers use perendoscopic biliary drainage as an efficient and safe alternative to surgery to treat AE biliary complications. Insertion of multiple plastic stents delays stent occlusion and leads to effective and prolonged bile duct patency