Genome-Wide Copy Number Analysis Uncovers a New HSCR Gene: NRG3

摘要: Hirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess contribution copy number variants (CNVs) to HSCR, we analysed data generated from our previous genome-wide association study on HSCR patients, whereby identified NRG1 as new susceptibility locus. Analysis 129 Chinese patients and 331 ethnically matched controls showed that have greater burden rare CNVs (p = 1.50×10−5), particularly for those encompassing genes 5.00×10−6). Our 246 rare-genic exclusive patients. Among those, detected NRG3 deletion 1.64×10−3). Subsequent follow-up (96 additional 220 controls) revealed 9 deletions (combined p 3.36×10−5) 2 de novo duplications among two controls. Importantly, paralog NRG1. Stratification presence/absence HSCR–associated syndromes while syndromic–HSCR carried significantly longer than non-syndromic or were enriched in CNV when compared 4.00×10−6) syndromic counterpart. results suggest role etiology provide insights into relative structural both HSCR. This would be first catalog