Related Experiment Video
Updated: May 19, 2026
In Vivo Modeling of the Morbid Human Genome using Danio rerio
Published on: August 24, 2013
Genetical analysis of all Danish patients diagnosed with chronic granulomatous disease
M A Jakobsen1, T L Katzenstein, N H Valerius
1Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. marianne.jakobsen@ouh.regionsyddanmark.dk
Insights
Genetic characterization of 27 Danish patients with Chronic Granulomatous Disease (CGD) identified mutations in key NADPH oxidase components. This study advances understanding of CGD genetics and provides a foundation for improved diagnostics.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Chronic Granulomatous Disease (CGD) is a rare inherited primary immunodeficiency.
- CGD results from defects in the NADPH oxidase enzyme complex, impairing phagocyte killing of microbes.
- Mutations in CYBB, CYBA, NCF1, NCF2, and NCF4 genes cause CGD.
Purpose of the Study:
- To genetically characterize a cohort of Danish patients with CGD.
- To identify the specific genetic mutations responsible for CGD in this patient group.
- To contribute to the understanding of CGD genetic heterogeneity.
Main Methods:
- Collection of samples from all Danish CGD patients diagnosed or followed over a 5-year period.
- Genetic characterization of 27 patients to identify causative mutations.
- Analysis of mutations in X-linked CYBB and autosomal CYBA, NCF1, NCF2, and NCF4 genes.
Main Results:
- The cohort comprised 27 patients, including 10 males with X-linked CGD and one female with skewed X-inactivation.
- Mutations were identified in CYBA (6 patients) and NCF1 (10 patients), including novel mutations.
- Three novel mutations were detected: a CYBA exon 6 deletion, a CYBB exon 8-13 duplication, and an NCF1 intron 7 splice site mutation.
Conclusions:
- Genetic analysis confirmed the underlying mutations in the studied Danish CGD cohort.
- The identification of novel mutations expands the known mutation spectrum for CGD.
- This genetic data is crucial for accurate diagnosis, genetic counseling, and potential therapeutic strategies for CGD.
Abstract:
Chronic granulomatous disease (CGD) is a rare inherited disorder of the innate immune system caused by a defect in NADPH oxidase, leaving the granulocytes unable to kill invading microorganisms. CGD is caused by mutation in one of the five components gp91phox, p22phox, p47phox, p67phox and p40phox, encoded by the X-linked CYBB gene and the autosomal CYBA, NCF1, NCF2 and NCF4 genes respectively. We have collected samples from all Danish patients with known CGD followed in the clinic or newly diagnosed during a 5-year period, a cohort of 27 patients, and characterized them genetically. The cohort includes 10 male patients with X-linked CGD and one female with extremely lyonized expression of a defective CYBB allele. Six patients had mutation in CYBA. Seven of 10 patients with a defect in NCF1 were homozygous for the common GT deletion, one was compound heterozygous for the GT deletion and a splice-site mutation, and two patients were homozygous for a nonsense mutation in exon 7. Three novel mutations were detected, a deletion of exon 6 in CYBA, a duplication of exon 8-13 in CYBB and a splice site mutation in intron 7 of NCF1.
