1 research outputs found
A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease
Publisher's version (útgefin grein)
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.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 chipgenotyped 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).
Overall, we find that CYBC1 deficiency results in CGD characterized by colitis and a distinct
profile of infections indicative of macrophage dysfunction.We wish to thank the family of the two probands, as well as all the other individuals who
participated in the study and whose contribution made this work possible.Peer Reviewe