作者
Gudny A Arnadottir, Gudmundur L Norddahl, Steinunn Gudmundsdottir, Arna B Agustsdottir, Snaevar Sigurdsson, Brynjar O Jensson, Kristbjorg Bjarnadottir, Fannar Theodors, Stefania Benonisdottir, Erna V Ivarsdottir, Asmundur Oddsson, Ragnar P Kristjansson, Gerald Sulem, Kristjan F Alexandersson, Thorhildur Juliusdottir, Kjartan R Gudmundsson, Jona Saemundsdottir, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Paolo Manzanillo, Sigurjon A Gudjonsson, Gudmundur A Thorisson, Olafur Th Magnusson, Gisli Masson, Kjartan B Orvar, Hilma Holm, Sigurdur Bjornsson, Reynir Arngrimsson, Daniel F Gudbjartsson, Unnur Thorsteinsdottir, Ingileif Jonsdottir, Asgeir Haraldsson, Patrick Sulem, Kari Stefansson
发表日期
2018/10/25
期刊
Nature Communications
卷号
9
期号
1
页码范围
4447
出版商
Nature Publishing Group UK
简介
Mutations in genes encoding subunits of the phagocyte NADPH oxidase complex are recognized to cause chronic granulomatous disease (CGD), a severe primary immunodeficiency. Here we describe how deficiency of CYBC1, a previously uncharacterized protein in humans (C17orf62), leads to reduced expression of NADPH oxidase’s main subunit (gp91phox) and results in CGD. Analyzing two brothers diagnosed with CGD we identify a homozygous loss-of-function mutation, p.Tyr2Ter, in CYBC1. Imputation of p.Tyr2Ter into 155K chip-genotyped Icelanders reveals six additional homozygotes, all with signs of CGD, manifesting as colitis, rare infections, or a severely impaired PMA-induced neutrophil oxidative burst. Homozygosity for p.Tyr2Ter consequently associates with inflammatory bowel disease (IBD) in Iceland (P = 8.3 × 10−8; OR = 67.6), as well as reduced height (P = 3.3 × 10−4; −8.5 cm …
学术搜索中的文章
GA Arnadottir, GL Norddahl, S Gudmundsdottir… - Nature Communications, 2018