Hematologically important mutations: The autosomal forms of chronic granulomatous disease (third update)

Roos, Dirk; Leeuwen, Karin van; Hsu, Amy P.; Priel, Debra Long; Begtrup, Amber; Brandon, Rhonda; Rawat, Amit; Vignesh, Pandiarajan; Madkaikar, Manesha; Stasia, Marie José; Bakri, Faris G.; Boer, Martin de; Roesler, Joachim; Köker, Nezihe; Köker, Mustafa Yavuz; Jakobsen, Marianne Antonius; Bustamante, Jacinta; García-Morato, María Bravo; Shephard, Juan Luis Valdivieso; Çağdaş, Deniz; Tezcan, İlhan; Sherkat, Roya; Mortaz, Esmaeil; Fayezi, Abbas; Shahrooei, Mohammad; Wolach, Baruch; Blancas-Galicia, Lizbeth; Kanegane, Hirokazu; Kawai, Toshinao; Condino‐Neto, Antônio; Vihinen, Mauno; Zerbe, Christa S.; Holland, Steven M.; Malech, Harry L.; Gallin, John I.; Kuhns, Douglas B.

doi:10.1016/j.bcmd.2021.102596

Cited by 31 publications

(31 citation statements)

References 104 publications

(42 reference statements)

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“…We evaluated four amino acid residues (Leu-51, Leu-52, Glu-53, and Pro-55) in the amino acid sequence that corresponds to exon 3 ( Fig. 1 A) based on the fact that the L51Q, L52P, E53V, and P55R mutations lead to the A22° type of CGD [ 16 ]. Because the amino acid substitutions may interfere with the recognition of p22 phox mutant proteins by anti-p22 phox mouse monoclonal antibody [mAB (CS9)] or rabbit polyclonal antibody, wild-type (wt) p22 phox and mutant proteins were prepared with a C-terminal Myc tag (p22 phox –Myc), which is detectable with mAB 9E10 (anti-Myc mouse monoclonal antibody).…”

Section: Resultsmentioning

confidence: 99%

“…A22° is the CGD phenotype. The “A” letter and “22” number refer to a utosomal recessive and p 22 phox and the superscript ° indicates whether the p22 phox protein is absent based on immunoblotting [ 16 ]. Five missense mutations are located in exon 3 (L51Q, L52P, E53V, and P55R) and exon 4 (R90Q).…”

Section: Resultsmentioning

confidence: 99%

“…In the absence of p22 phox , the Nox2 monomer is degraded by ER-associated degradation (ERAD) [ 10 , 13 , 14 ]. This explains why Nox2 protein is undetectable in the background of p22 phox ( CYBA gene) genetic deficiency [ [15] , [16] , [17] ]. Thus, heterodimerization with p22 phox appears to promote proper the folding of Nox2 to evade degradation by ERAD.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, Pro-156 is considered to be responsible for the activation of Nox2. The mutational hotspot located in CYBA exon 3 in the A22° type (wherein the p22 phox protein is undetectable) of CGD exhibits missense mutations in p22 phox (L51Q, L52P, E53V, and P55R) [ 16 ]; however, to the best of our knowledge, these mutations have not been characterized yet. In the present study, we characterized missense mutations in p22 phox (L51Q, L52P, E53V, and P55R) and demonstrated that these amino acid substitutions promote the degradation of p22 phox protein in the ER.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Derlin-1-mediated degradation of NADPH oxidase partner p22 by thiol modification

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of Derlin-1-mediated degradation of NADPH oxidase partner p22 by thiol modification

et al. 2022

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“…This IEI was estimated to affect 1/200,000 to 1/250,000 newborns, with majority of the cases caused by X-linked CYBB mutations ( 27 ). Monogenic defects in CYBA , CYBC1 , NCF1 , NCF2 and NCF4 led to the less common form of CGD inherited in autosomal recessive pattern ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing

et al. 2021

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Blended phenotypes exhibited by a patient may present a challenge to the establishment of diagnosis. In this study, we report a seven-year-old Murut girl with unusual features of Williams-Beuren syndrome (WBS), including recurrent infections and skin abscesses. Considering the possibility of a second genetic disorder, a mutation screening for genes associated with inborn errors of immunity (IEI) was conducted using whole exome sequencing (WES). Analysis of copy number variations (CNVs) from the exome data revealed a 1.53Mb heterozygous deletion on chromosome 7q11.23, corresponding to the known WBS. We also identified a biallelic loss of NCF1, which indicated autosomal recessive chronic granulomatous disease (CGD). Dihydrorhodamine (DHR) flow cytometric assay demonstrated abnormally low neutrophil oxidative burst activity. Coamplification of NCF1 and its pseudogenes identified a GT-deletion (ΔGT) at the start of exon 2 in NCF1 (NM_000265.7: c.75_76delGT: p.Tyr26Hisfs*26). Estimation of NCF1-to-NCF1 pseudogenes ratio using ΔGT and 20-bp gene scans affirmed nil copies of NCF1 in the patient. While the father had a normal ratio of 2:4, the mother had a ratio of 1:5, implicating the carrier of ΔGT-containing NCF1. Discovery of a 7q11.23 deletion involving one NCF1 allele and a ΔGT in the second NCF1 allele explained the coexistence of WBS and CGD in our patient. This study highlights the capability of WES to establish a molecular diagnosis for a case with blended phenotypes, enabling the provision of appropriate prophylactic treatment.

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Paradigm Shifts in the History of Nox2 and Its Regulators: An Appreciative Critique

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NADPH Oxidases Revisited: From Function to Structure

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Hematologically important mutations: The autosomal forms of chronic granulomatous disease (third update)

Cited by 31 publications

References 104 publications

Regulation of Derlin-1-mediated degradation of NADPH oxidase partner p22 by thiol modification

Regulation of Derlin-1-mediated degradation of NADPH oxidase partner p22 by thiol modification

Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing

Paradigm Shifts in the History of Nox2 and Its Regulators: An Appreciative Critique

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