13 research outputs found
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
76-year old patient with suspected but not confirmed “idiopathic myelofibrosis”
Feld C, Spangenberger H, Böhm J, Meuthen D, Meuthen I. 76-jähriger Patient mit nicht bestätigtem Verdacht auf „idiopathische Myelofibrose“. Der Internist. 2011;52(11):1346-1350.Ein 76-jähriger Patient wurde mit Hepatosplenomegalie, Anämie, Thrombopenie, Eosinophilie, Erhöhung der Laktatdehydrogenase und erythroleukämischem Blutbild stationär aufgenommen. Die Knochenmarkhistologie, die Immunhistologie und der molekulargenetische Nachweis der c-kit-Mutation D816 V belegten eine systemische Mastozytose. Eine auswärts vermutete idiopathische Myelofibrose lag nicht vor. Nach Gabe von Prednison erholte sich das Blutbild, der Allgemeinzustand des Patienten besserte sich rasch
Quantum interference and statistical fluctuations in deep inelastic heavy-ion reactions
SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman
Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
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