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

Fecal neopterin level determination: can be a useful screening test for colorectal polyps?

Background Colorectal cancer (CRC) is a leading cause of cancer death worldwide. The main precursor lesion leading to CRC is the adenomatous colorectal polyp (CP). Nowadays, there is no recognized perfect screening test of CP and CRC. Neopterin is an important marker of cellular inflammation. In this study, we aimed to evaluate comparatively immunochromatographic fecal occult blood test (iFOBT) and fecal neopterin levels (FNLs) in patients with CP and controls. Methods One hundred eleven patients diagnosed with CP and 68 individuals with negative colonoscopy were included in the study. iFOBT and FNLs were assessed in patients and controls. Results FNLs and iFOBT positivity were significantly higher in patients with CP than in controls (17.15 +/- 3.55 mu mol/L/g vs. 12.25 +/- 2.19 mu mol/L/g, P = 0.00 and 46.8% vs. 14.8%, P = 0.00, respectively). FNLs were significantly higher in cases with adenomatous polyps than in hyperplastic polyps (P = 0.002). FNL >= 14.00 mu mol/L/g was the best cutoff value to differentiate between patients with CP from controls (P = 0.000). A multiple logistic regression analysis showed that high FNL was positively correlated with presence, number, diameter of CPs, and presence of adenoma (P 0.005). The sensitivity of high FNL for CP was 81.1%, which was superior to iFOBT positivity (47.7%, P 0.001). Discussion FNL level is significantly increased in CPs. The FNL exhibited increased sensitivity for identifying CP and adenomatous lesions compared with iFOBT. FNL determination could have as a new screening and diagnostic test for CP