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06.02.2018 | Original Article

Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A)

verfasst von: Baruch Wolach, Ronit Gavrieli, Martin de Boer, Karin van Leeuwen, Ofir Wolach, Galia Grisaru-Soen, Arnon Broides, Amos Etzioni, Raz Somech, Dirk Roos

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2018

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Abstract

Purpose

Chronic granulomatous disease (CGD) is an innate immune deficiency disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex that impair the synthesis of oxygen radicals, thus rendering patients susceptible to recurrent infections and excessive hyperinflammatory responses. The most common autosomal recessive form of CGD is p47^phox deficiency, which is often clinically milder than the more common X-linked recessive form. Here, we report data on genetics, clinical and biochemical findings in 17 CGD patients of Kavkazi origin with the nonsense mutation c.579G>A in the NCF1 gene, leading to p47^phox deficiency.

Methods

Diagnosis was based on detailed clinical evaluation, respiratory burst activity by cytochrome c reduction and dihydrorhodamine-1,2,3 (DHR) assay by flow cytometry, expression of p47^phox by immunoblotting and molecular confirmation by DNA sequence analysis.

Results

Twelve male and five female patients with median age at onset of 2.5 years (range 1 day to 9 years) were included in the study. The present cohort displays an encouraging 88% overall long-term survival, with median follow-up of 17 years. Clinical manifestations varied from mild to severe expression of the disease. Correlation between genotype and phenotype is unpredictable, although the Kavkazi patients were more severely affected than other patients with p47^phox deficiency.

Conclusions

Kavkazi CGD patients harbor a common genetic mutation that is associated with a heterogeneous clinical phenotype. Early diagnosis and proper clinical management in an experienced phagocytic leukocyte center is imperative to ensure favorable patient outcome. New treatment strategies are ongoing, but results are not yet conclusive.

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Titel: Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A)
verfasst von: Baruch Wolach
Ronit Gavrieli
Martin de Boer
Karin van Leeuwen
Ofir Wolach
Galia Grisaru-Soen
Arnon Broides
Amos Etzioni
Raz Somech
Dirk Roos
Publikationsdatum: 06.02.2018
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 2/2018
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-018-0475-1

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