Novel NCF2 Mutation Causing Chronic Granulomatous Disease
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ORIGINAL ARTICLE
Novel NCF2 Mutation Causing Chronic Granulomatous Disease Idit Lachover Roth 1 & Pazit Salamon 2 & Tal Freund 3 & Yael Ben-David Gadot 4,5 & Szilvia Baron 6 & Tova Hershkovitz 5,7 & Irit Shefler 2 & Suhair Hanna 5,8 & Ronit Confino-Cohen 1 & Lea Bentur 4,5 & David Hagin 3 Received: 10 April 2020 / Accepted: 30 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in the NADPH oxidase complex. Mutations in NCF2 encoding the cytosolic factor p67phox result in autosomal recessive CGD. We describe three patients with a novel c.855G>C NCF2 mutation presenting with diverse clinical phenotype. Two siblings were heterozygous for the novel mutation and for a previously described exon 8–9 duplication, while a third unrelated patient was homozygous for the novel mutation. Mutation pathogenicity was confirmed by abnormal DHR123 assay and absent p67phox production and by sequencing of cDNA which showed abnormal RNA splicing. Clinically, the homozygous patient presented with suspected early onset interstitial lung disease and NCF2 mutation was found on genetic testing performed in search for surfactant-related defects. The two siblings also had variable presentation with one having history of severe pneumonia, lymphadenitis, and recurrent skin abscesses and the other presenting in his 30s with discoid lupus erythematosus and without significant infectious history. We therefore identified a novel pathogenic NCF2 mutation causing diverse and unusual clinical phenotype. Keywords Chronic granulomatous disease . CGD . primary immunodeficiency disorders . PIDD . inborn errors of immunity . IEI . childhood interstitial lung disease . NCF2 . P67Phox
Introduction Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder with an estimated incidence of
approximately 1:250,000 [1, 2], caused by defects in components of the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The resulting abnormal NADPH oxidase activity leads to diminished production of reactive
Idit Lachover Roth, Pazit Salamon and Tal Freund contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00820-8) contains supplementary material, which is available to authorized users. * David Hagin [email protected]
Tova Hershkovitz [email protected]
Idit Lachover Roth [email protected]
Irit Shefler [email protected]
Pazit Salamon [email protected]
Suhair Hanna [email protected]
Tal Freund [email protected] Yael Ben-David Gadot [email protected] Szilvia Baron [email protected]
Ronit Confino-Cohen [email protected] Lea Bentur [email protected] Extended author information available on the last page of the article
J Clin Immunol
oxygen species (ROS), which act either directly [3] or through induction of potassium influx and acti
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