A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease

doi:10.1038/s41467-018-04520-1

GSTDTAP > 资源环境科学

DOI	10.1038/s41467-018-04520-1
	A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease
	Arnadottir, Gudny A.1; Norddahl, Gudmundur L.1; Gudmundsdottir, Steinunn 1; Agustsdottir, Arna B.1; Sigurdsson, Snaevar 1; Jensson, Brynjar O.1; Bjarnadottir, Kristbjorg 1; Theodors, Fannar 1; Benonisdottir, Stefania 1; Ivarsdottir, Erna V.1,2; Oddsson, Asmundur 1; Kristjansson, Ragnar P.1; Sulem, Gerald 1; Alexandersson, Kristjan F.1; Juliusdottir, Thorhildur 1; Gudmundsson, Kjartan R.1; Saemundsdottir, Jona 1; Jonasdottir, Adalbjorg 1; Jonasdottir, Aslaug 1; Sigurdsson, Asgeir 1; Manzanillo, Paolo 1; Gudjonsson, Sigurjon A.1; Thorisson, Gudmundur A.1; Magnusson, Olafur Th.1; Masson, Gisli 1; Orvar, Kjartan B.3,4; Holm, Hilma 1; Bjornsson, Sigurdur 3,4; Arngrimsson, Reynir 5,6; Gudbjartsson, Daniel F.1,2; Thorsteinsdottir, Unnur 1,6; Jonsdottir, Ingileif 1,6; Haraldsson, Asgeir 6,7; Sulem, Patrick 1; Stefansson, Kari 1,6
	2018-10-25
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2018
卷号	9
文章类型	Article
语种	英语
国家	Iceland
英文摘要	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 (gp91(phox)) 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 x 10(-8); OR = 67.6), as well as reduced height (P = 3.3 x 10(-4); -8.5 cm). Overall, we find that CYBC1 deficiency results in CGD characterized by colitis and a distinct profile of infections indicative of macrophage dysfunction.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000448265400004
WOS关键词	INFLAMMATORY-BOWEL-DISEASE ; MYCOBACTERIUM-TUBERCULOSIS ; LEGIONELLA-PNEUMOPHILA ; HUMAN KNOCKOUTS ; NADPH OXIDASE ; CATALASE ; GENE ; VARIANTS ; PROTEIN ; MACROPHAGES
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/203829
专题	资源环境科学
作者单位	1.Amgen Inc, deCODE Genet, Reykjavik, Iceland; 2.Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland; 3.Landspitali Univ Hosp, Dept Internal Med, Reykjavik, Iceland; 4.Glaesibae, Med Ctr, Reykjavik, Iceland; 5.Landspitali Univ Hosp, Dept Genet & Mol Med, Reykjavik, Iceland; 6.Univ Iceland, Fac Med, Reykjavik, Iceland; 7.Childrens Hosp Iceland, Landspitali Univ Hosp, Reykjavik, Iceland
推荐引用方式 GB/T 7714	Arnadottir, Gudny A.,Norddahl, Gudmundur L.,Gudmundsdottir, Steinunn,et al. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease[J]. NATURE COMMUNICATIONS,2018,9.
APA	Arnadottir, Gudny A..,Norddahl, Gudmundur L..,Gudmundsdottir, Steinunn.,Agustsdottir, Arna B..,Sigurdsson, Snaevar.,...&Stefansson, Kari.(2018).A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease.NATURE COMMUNICATIONS,9.
MLA	Arnadottir, Gudny A.,et al."A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease".NATURE COMMUNICATIONS 9(2018).