Dataset Information

Inherited p40phox deficiency differs from classic chronic granulomatous disease.

ABSTRACT: Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.

SUBMITTER: van de Geer A

PROVIDER: S-EPMC6118590 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Inherited p40phox deficiency differs from classic chronic granulomatous disease.

van de Geer Annemarie A Nieto-Patlán Alejandro A Kuhns Douglas B DB Tool Anton Tj AT Arias Andrés A AA Bouaziz Matthieu M de Boer Martin M Franco José Luis JL Gazendam Roel P RP van Hamme John L JL van Houdt Michel M van Leeuwen Karin K Verkuijlen Paul Jh PJ van den Berg Timo K TK Alzate Juan F JF Arango-Franco Carlos A CA Batura Vritika V Bernasconi Andrea R AR Boardman Barbara B Booth Claire C Burns Siobhan O SO Cabarcas Felipe F Bensussan Nadine Cerf NC Charbit-Henrion Fabienne F Corveleyn Anniek A Deswarte Caroline C Azcoiti María Esnaola ME Foell Dirk D Gallin John I JI Garcés Carlos C Guedes Margarida M Hinze Claas H CH Holland Steven M SM Hughes Stephen M SM Ibañez Patricio P Malech Harry L HL Meyts Isabelle I Moncada-Velez Marcela M Moriya Kunihiko K Neves Esmeralda E Oleastro Matias M Perez Laura L Rattina Vimel V Oleaga-Quintas Carmen C Warner Neil N Muise Aleixo M AM López Jeanet Serafín JS Trindade Eunice E Vasconcelos Julia J Vermeire Séverine S Wittkowski Helmut H Worth Austen A Abel Laurent L Dinauer Mary C MC Arkwright Peter D PD Roos Dirk D Casanova Jean-Laurent JL Kuijpers Taco W TW Bustamante Jacinta J

The Journal of clinical investigation 20180806 9

Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the muta ...[more]

PMID: 29969437

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Dataset Information

Inherited p40phox deficiency differs from classic chronic granulomatous disease.

Publications

Inherited p40phox deficiency differs from classic chronic granulomatous disease.

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