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Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.
- Source :
- Nature communications, Vol. 11, no. 1, p. 995 (2020)
- Publication Year :
- 2020
-
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), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.
Details
- Database :
- OAIster
- Journal :
- Nature communications, Vol. 11, no. 1, p. 995 (2020)
- Notes :
- English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1288275785
- Document Type :
- Electronic Resource