Female CYBB Mutation Mosaicism Leading to Inheritance of X-linked Chronic Granulomatous Disease / 罕见病研究

Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency characterized by severe bacterial and fungal infections and tissue granuloma formation early in life. Diagnosis of CGD involves the granulocyte function assays and gene mutation analysis. X-linked CGD (XL-CGD) caused by gene defects of CYBB is the most prevalent type of CGD. The clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD were reported here. The patient is a 7-year-old boy manifested as recurrent lower respiratory tract infection and failed to thrive. The patient had a history of osteo- myelitis and perianal abscess, with Bacille Calmette-Guérin (BCG) vaccine complications. Respiratory burst of neutrophils was measured with DHR oxidation assay and the histogram showing no significant change in neutrophil fluorescence after stimulation of the patient and the mother's histogram had a pattern of 2 peaks after stimulation. A heterozygous mutation in the CYBB gene (c.866G > A, p.W289X) was identified through inheritance from the patient's mother. Genetic analysis from blood and cheek mucosal cells indicated the female was a mosaicism in CYBB with mutation was present in about 19.5% of her leukocytes. We reported the clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD for the first time in China to enrich the understanding of XL-CGD and provide new sights for the hereditary counseling.

The analysis CYBB gene mutation and prenatal diagnosis in X-linked chronic granulomatous disease / 临床儿科杂志

Objective To analyze the clinical feature of X-linked chronic granulomatous disease (X-CGD) and gene mutation of CYBB. Method The clinical data of X-CGD in one child and the results of CYBB gene detection in his family were reviewed. Results This boy had onset in the neonatal period and presented with recurrent severe pulmonary infection as his main manifestation. Results of nitroblue tetrazolium test (NBT) in both non-stimulation group and LPS stimulation group in the child were 0, and neutrophil oxidation index (NOI) was 1.15. Gene analysis showed a deletion mutation in exon 6 of CYBB gene in the child (579-582delATTA), which resulted in frameshift mutation started from coding sequence of 189—isoleucine (I) and stop codon occured in advance in the 212th amino acid (I189fsX212). Both the child's mother and grandmother were carriers of the mutated gene. The same deletion mutation was not found in the CYBB gene in the amniocyte from the mother's next child. Conclusion One case of X-CGD patient with CYBB gene mutation and his families were diagnosed by gene detection. Prenatal diagnosis can avoid the birth of children with X-CGD.

Identification of a Novel Mutation in the CYBB Gene, p.Asp378Gly, in a Patient With X-linked Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare immunodeficiency disease, which is characterized by the lack of a functional nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. The disease presents leukocytosis, anemia, hypergammaglobulinemia, and granuloma formation of the skin, lung, or lymph nodes. The mutation of the CYBB gene encoding gp91phox, located on chromosome Xp21.1 is one of the causes of CGD. We report a patient with X-linked CGD who carried a novel mutation, a c.1133A>G (paAsp378Gly) missense mutation, in the CYBB gene.

Identification of a Novel Mutation in the CYBB Gene, p.Asp378Gly, in a Patient With X-linked Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare immunodeficiency disease, which is characterized by the lack of a functional nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. The disease presents leukocytosis, anemia, hypergammaglobulinemia, and granuloma formation of the skin, lung, or lymph nodes. The mutation of the CYBB gene encoding gp91phox, located on chromosome Xp21.1 is one of the causes of CGD. We report a patient with X-linked CGD who carried a novel mutation, a c.1133A>G (paAsp378Gly) missense mutation, in the CYBB gene.

Clinical features and CYBB gene mutation analysis of chronic granulomatous disease in 6 neonate infants / 中华实用儿科临床杂志

Objective To determine the clinical features and gene expression of neonatal chronic granulomatous disease(CGD) in newborns,in order to provide the evidence for early diagnosis,treatment and infection prophylaxis and so as to improve prognosis.Methods The clinical data of 6 neonates with CGD who hospitalized in Beijing Children's Hospital,Capital University of Medical Sciences,from Jan.to Dec.2013 were retrospectively analyzed,to summarize their clinical features and gene expression.Results All patients were male,mean age of onset in 6 patients was 19 days old.Six patients were onset with cough and fever,3 cases with skin abscesses.All patients had special lung images and their respiratory burst test were all positive.Six patients were all X-linked recessive heredity with mutation in CYBB gene,4 cases carried missense mutation,1 case carried frameshit mutation,1 case had shear point disappear.All patients were improved during hospitalization with anti-infective therapy including antifungal and antibiotic drugs.After their discharge,the patients were followed up for 1 year,among them 5 patients taking antibiotics according to doctor's advise hadn't got any severe infections or other complications,1 patient did not receive antibiotics according to doctor's advise,caught respiratory infection was occured once per 1-2 months and died of multiple organ failure in 5 months due to severe infection.Conclusions For newborn with respiratory symptoms such as cough and fever,with apparently nodular and massive radiologic infiltrates,CGD cases should be highly suspected.Long term prognosis is good in children with prophylactic medication and they may have a longer infection interval.

Molecular Analysis of X-linked Chronic Granulomatous Disease in Five Unrelated Korean Patients

Chronic granulomatous disease (CGD) is a fatal genetic disorder in which phagocytes fail to produce antimicrobial superoxide because of NADPH oxidase deficiency. Molecular defects in CYBB gene causing X-linked CGD are responsible for about 70% of all cases. This study was done to confirm genetic defects of CYBB gene in five Korean patients who were highly suggestive of having CGD by clinical history. We performed initial screening for five unrelated Korean patients using single strand conformation polymorphism (SSCP) and then selective sequencing for the regions involving the abnormal bands. Activated NBT tests revealed that all patients were X-linked. SSCP analysis for CYBB gene showed abnormal bands in all patients. The molecular defects of five patients were as follows: c.1663insT, c.1111-1G>T, c.39_40insG, c.927delC and c.434T>C mutation. This result will help the families with prenatal diagnosis or genetic counseling.