Clinical, functional and genetic characterization of 16 patients suffering from chronic granulomatous disease variants – identification of 11 novel mutations in<i>CYBB</i>

Mollin, Michelle; Beaumel, Sylvain; Vigne, Bénédicte; Brault, Julie; Roux-Buisson, Nathalie; Rendu, John; Barlogis, Vincent; Catho, G.; Dumeril, C.; Fouyssac, Fanny; Monnier, Delphine; Gandemer, Virginie; Revest, Matthieu; Jp, Brion; Bost-Bru, C.; Jeziorski, Éric; Eitenschenck, Laurence; Jarrasse, Clemence; Haus, Susanne; Houachée-Chardin, M; Hancart, M.; Gautier, Michel; Bertrand, Yves; Plantaz, Dominique; Kelečić, Jadranka; Traberg, Rasa; Kainulainen, Leena; Fauré, Julien; Fieschi, Franck; Stasia, Marie José

doi:10.1111/cei.13520

Cited by 18 publications

(14 citation statements)

References 54 publications

(80 reference statements)

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“…The finding in the present study on lower densities of NOX2positive cells in periodontitis lesions of current smokers indicates a disturbance in neutrophil functions, including the formation of neutrophil extracellular traps (NETs) and the elimination of pathogens through the "respiratory burst" process. 32,33 As NOX2 is part of the NADPH-oxidase family, studies showing associations between genetic polymorphisms of NADPH-oxidase and the condition "aggressive periodontitis" of the former classification are of interest (e.g., Nibali et al 34 ).…”

Section: Re Sultsmentioning

confidence: 99%

Cellular expression of epigenetic markers and oxidative stress in periodontitis lesions of smokers and non‐smokers

Dionigi

Larsson

Difloe‐Geisert

et al. 2022

J of Periodontal Research

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Objective To evaluate differences in the cellular expression of epigenetic markers and oxidative stress in periodontitis lesions between current smokers and non‐smokers. Background Tobacco smoking is recognized as one of the major risk factors for periodontitis. However, the mechanisms by which smoking affects the progression of the disease remain to be determined. Methods Twenty‐five current smokers and 21 non‐smokers with generalized severe periodontitis were included. From each patient, one soft tissue biopsy from a periodontitis site was harvested and prepared for histological analysis. The infiltrated connective tissue (ICT) was selected as the region of interest to assess the cellular expression of epigenetic markers and reactive oxygen/nitrogen species (RONS) by immunohistochemistry. Results Although the ICT of smokers and non‐smokers did not differ in size or in the expression of markers for DNA damage or oxidative stress, current smokers presented with significantly lower area proportions and densities of cells positive for the epigenetic markers DNMT1 and AcH3. In addition, periodontitis lesions in current smokers presented with a diminished antimicrobial activity, as indicated by significantly lower densities and area proportions of NOX2‐ and iNOS‐positive cells. Conclusions Components of the host response and epigenetic mechanisms in periodontitis lesions in smokers are downregulated as opposed to lesions of non‐smokers.

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Section: Re Sultsmentioning

confidence: 99%

Cellular expression of epigenetic markers and oxidative stress in periodontitis lesions of smokers and non‐smokers

Dionigi

Larsson

Difloe‐Geisert

et al. 2022

J of Periodontal Research

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“…Monoclonal antibody (mab) 7D5 directed against external epitopes of gp91 phox (NOX2) (D162-3, Clinisciences, Nanterre, France), monoclonal anti-p22 phox (SC-130550, Santa Cruz Biotechnologies Inc, Heidelberg, Germany), monoclonal anti-p67 phox (AB109523/EPR5065, Abcam, Paris, France) and monoclonal anti-p47 phox (AB179457/EPR 13134, Abcam, Paris, France) with secondary antibody conjugated with Alexa-Fluor 488 (A11070, Invitrogen Life technologies, Villebon sur Yvette, France) or PE (A10543, Invitrogen Life Technologies, Villebon sur Yvette, France), were used for analysis of NADPH oxidase subunit expression in phagocytic cells (2 × 10 5 cells). In case of p22 phox , p47 phox , or p67 phox expression analysis, neutrophils were previously fixed in PFA 2% (v/v) and then incubated with specific antibodies directed against p22 phox , p47 phox , or (38). Control staining with appropriate isotype-matched control antibodies was included to establish thresholds for positive staining.…”

Section: Analysis Of the Expression Of Nadph Oxidase Components By Flmentioning

confidence: 99%

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

et al. 2021

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Chronic granulomatous Disease (CGD) is a rare innate immunodeficiency disorder caused by mutations in one of the six genes (CYBA, CYBB, NCF1, NCF2, NCF4, and CYBC1/EROS) encoding the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH)—oxidase complex in phagocytes. In the Western population, the most prevalent form of CGD (about two-thirds of all cases) is the X-linked form (X-CGD) caused by mutations in CYBB. The autosomal recessive forms (AR-CGD), due to mutations in the other genes, collectively account for the remaining one-third of CGD cases. We investigated the clinical and molecular features of 22 Jordanian, 7 Libyan, and 2 Iraqi CGD patients from 21 different families. In addition, 11 sibling patients from these families were suspected to have been died from CGD as suggested by their familial and clinical history. All patients except 9 were children of consanguineous parents. Most of the patients suffered from AR-CGD, with mutations in CYBA, NCF1, and NCF2, encoding p22phox, p47phox, and p67phox proteins, respectively. AR-CGD was the most frequent form, in Jordan probably because consanguineous marriages are common in this country. Only one patient from non-consanguineous parents suffered from an X910 CGD subtype (0 indicates no protein expression). AR670 CGD and AR220 CGD appeared to be the most frequently found sub-types but also the most severe clinical forms compared to AR470 CGD. As a geographical clustering of 11 patients from eight Jordanian families exhibited the c.1171_1175delAAGCT mutation in NCF2, segregation analysis with nine polymorphic markers overlapping NCF2 indicates that a common ancestor has arisen ~1,075 years ago.

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“…Congenital defects of phagocyte, bone marrow failure & phenocopies of PIDD Among congenital defects of phagocytes, congenital neutropenias, defects of motility, defects of respiratory burst and other non-lymphoid defects are included. Mutations in different genes such as CYBB and NCF1 lead to phagocyte defects of NADPH oxidase activity causing chronic granulomatous disease [51]. Pathogenic mutations are found in 50% of cases with bone marrow failure, herein the importance of conducting genetic studies in such patients [52].…”

Section: Complement Deficienciesmentioning

confidence: 99%

Functional Genetics in Inborn Errors of Immunity

Rey-Jurado

Poli

2021

Future Rare Dis.

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Inborn errors of immunity are genetic defects of the immune system, causing increased susceptibility to infection, autoinflammation, autoimmunity and immune dysregulation. Next-generation sequencing has enabled exponential identification of novel inborn errors of immunity due to mutations in genes encoding for proteins that participate in the immune response. However, genomic sequencing often yields multiple variants in potential candidate genes, hence functional validation of these genetic defects becomes paramount to achieve diagnosis and discovery. Genome-editing technologies such as CRISPR-Cas9 have allowed exponential advances on discovery of new primary immunodeficiencies, enabling appropriate diagnosis and treatment. This review summarizes the heterogeneous clinical presentation of primary immunodeficiencies and contextualizes the rationale for functional validation studies to achieve diagnosis and discovery, subsequently leading to the application of directed therapies.

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Clinical, functional and genetic characterization of 16 patients suffering from chronic granulomatous disease variants – identification of 11 novel mutations inCYBB

Cited by 18 publications

References 54 publications

Cellular expression of epigenetic markers and oxidative stress in periodontitis lesions of smokers and non‐smokers

Cellular expression of epigenetic markers and oxidative stress in periodontitis lesions of smokers and non‐smokers

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

Functional Genetics in Inborn Errors of Immunity

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