The analysis of clinical manifestations and genetic mutations in childhood chronic granulomatous disease / 临床儿科杂志

Objective To explore the pathogenesis and diagnosis of chronic granulomatous disease. Methods Clinical features and laboratory examination results of a child with chronic granulomatous disease were retrospectively analyzed. Genome DNA was extracted from peripheral blood of the child and his parents. The high-throughput sequencing was performed by Illumina sequencing platform, using the Agilent SureSelect exome capture method. Results The child had recurrent infections along with liver enlargement and dysfunction. The anti-infection and symptomatic treatment were unsatisfactory. Gene sequencing analysis revealed a homozygous point mutation (c.7C?>?T, p.Gln3*) in CYBA gene. His mother had the same heterozygous mutation in this locus, and his father had a large fragment heterozygous deletions. No other candidate gene mutations were identiifed. Conclusions The diagnosis of chronic granulomatous disease is conifrmed in this child. It is caused by CYBA gene mutation.

Long-term outcome of patients with p22phox-deficient chronic granulomatous disease on Jeju Island, Korea / 소아과

PURPOSE: This study investigated the long-term clinical outcomes of patients with p22(phox)-deficient chronic granulomatous disease (CGD) on Jeju Island and retrospectively evaluated the effects of interferon-gamma (IFN-gamma) prophylaxis. METHODS: The medical records of 15 patients with CGD were retrospectively reviewed. The efficacy of IFN-gamma prophylaxis was evaluated by comparing the frequency of severe infections before and after starting continuous prophylaxis with IFN-gamma. RESULTS: At the time of the analysis, 14 patients were alive, with a median age of 14.3 years. The diagnosis of CGD was made at a median age of 2.4 years, and the median age at onset of severe infection was 0.3 years. Thirteen of the 15 patients had their first severe infection within the first year of life. The overall incidence of severe infection was 1.36 infections per patient-year; pneumonia, suppurative lymphadenitis, and skin and subcutaneous abscesses were the most common infections. Aspergillus species were the most frequently isolated microorganisms, present in 15.8% of isolates. IFN-gamma did not significantly change the rate of severe infection. The survival rate for patients after 2 years of age was 93%; there was a prolonged survival plateau beyond the age of 2. CONCLUSION: Compared with cases of X-linked CGD reported in other studies, patients with CGD on Jeju Island did not show obviously different clinical manifestations, but they had a significantly higher survival rate. Further studies with a substantially longer period of observation, and with more patients under intensive surveillance are necessary to elucidate the prophylactic efficiency of IFN-gamma.

Chronic Granulomatous Disease on Jeju Island, Korea

Chronic granulomatous disease (CGD) is a rare inherited disorder of a defective NADPH oxidase enzyme, resulting in very low or no production of superoxide and subsequent reactive oxygen species. Consequently, patients with CGD are highly susceptible to severe bacterial and fungal infections. CGD is a genetically heterogeneous disease caused by defects in any one of the genes encoding the NADPH oxidase components. CGD generally affects about 3-4 per 1,000,000 individuals; thus, it is surprising that the prevalence of CGD on Jeju Island is 34.3 per 1,000,000 individuals. At present, 20 patients with CGD from 14 unrelated families on Jeju Island have been identified; nine males and 11 females. All patients with CGD tested on Jeju Island had an identical and homozygous mutation (c.7C>T in CYBA, p.Q3X in p22phox). Therefore, all patients were autosomal recessive form of CGD. This strongly suggests that the unique and identical mutation in CYBA may be inherited from a common proband. Using mutation-specific primers to detect the mutated allele in CYBA, the frequency of subjects carrying a mutated allele was 1.3% of enrolled subjects from Seogwipo City. Further studies are necessary to elucidate how frequently this mutant allele occurs in the population on Jeju Island. Additionally, it is important to construct a national registry system to understand the pathophysiology of CGD and develop a strategy for long-term therapy.

Genetic Analysis of 10 Unrelated Korean Families with p22-phox-deficient Chronic Granulomatous Disease: An Unusually Identical Mutation of the CYBA Gene on Jeju Island, Korea

Chronic granulomatous disease (CGD) is a rare hereditary disorder characterized by recurrent life-threatening bacterial and fungal infections. The underlying defect in CGD is an inability of phagocytes to produce reactive oxygen species as a result of defects in NADPH oxidase. Considering that CGD generally affects about 3-4 in 1,000,000 individuals, it is surprising that the prevalence of CGD on Jeju Island is 20.7 in 1,000,000 individuals. We performed genetic analysis on 12 patients from 10 unrelated families and found that all patients had an identical homozygous single-base substitution of C to T in exon 1 (c.7C>T) of the CYBA gene, which was expected to result in a nonsense mutation (p.Q3X). Because Jeju Island has long been a geologically isolated region, the high prevalence of CGD on Jeju Island is presumably associated with an identical mutation inherited from a common ancestor or proband.