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A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease.
Arnadottir, Gudny A; Norddahl, Gudmundur L; Gudmundsdottir, Steinunn; Agustsdottir, Arna B; Sigurdsson, Snaevar; Jensson, Brynjar O; Bjarnadottir, Kristbjorg; Theodors, Fannar; Benonisdottir, Stefania; Ivarsdottir, Erna V; Oddsson, Asmundur; Kristjansson, Ragnar P; Sulem, Gerald; Alexandersson, Kristjan F; Juliusdottir, Thorhildur; Gudmundsson, Kjartan R; Saemundsdottir, Jona; Jonasdottir, Adalbjorg; Jonasdottir, Aslaug; Sigurdsson, Asgeir; Manzanillo, Paolo; Gudjonsson, Sigurjon A; Thorisson, Gudmundur A; Magnusson, Olafur Th; Masson, Gisli; Orvar, Kjartan B; Holm, Hilma; Bjornsson, Sigurdur; Arngrimsson, Reynir; Gudbjartsson, Daniel F; Thorsteinsdottir, Unnur; Jonsdottir, Ingileif; Haraldsson, Asgeir; Sulem, Patrick; Stefansson, Kari.
Afiliación
  • Arnadottir GA; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Norddahl GL; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Gudmundsdottir S; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Agustsdottir AB; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Sigurdsson S; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Jensson BO; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Bjarnadottir K; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Theodors F; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Benonisdottir S; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Ivarsdottir EV; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Oddsson A; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
  • Kristjansson RP; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Sulem G; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Alexandersson KF; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Juliusdottir T; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Gudmundsson KR; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Saemundsdottir J; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Jonasdottir A; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Jonasdottir A; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Sigurdsson A; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Manzanillo P; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Gudjonsson SA; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Thorisson GA; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Magnusson OT; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Masson G; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Orvar KB; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Holm H; Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland.
  • Bjornsson S; The Medical Center, Glaesibae, Reykjavik, Iceland.
  • Arngrimsson R; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Gudbjartsson DF; Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland.
  • Thorsteinsdottir U; The Medical Center, Glaesibae, Reykjavik, Iceland.
  • Jonsdottir I; Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.
  • Haraldsson A; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Sulem P; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Stefansson K; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
Nat Commun ; 9(1): 4447, 2018 10 25.
Article en En | MEDLINE | ID: mdl-30361506
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). Overall, we find that CYBC1 deficiency results in CGD characterized by colitis and a distinct profile of infections indicative of macrophage dysfunction.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación con Pérdida de Función / Enfermedad Granulomatosa Crónica Tipo de estudio: Etiology_studies Límite: Child / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Islandia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación con Pérdida de Función / Enfermedad Granulomatosa Crónica Tipo de estudio: Etiology_studies Límite: Child / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Islandia Pais de publicación: Reino Unido