Clinical and molecular characteristics of Thai families with autosomal recessive chronic granulomatous disease

ABSTRACT

Background: Autosomal recessive chronic granulomatous disease (AR-CGD) is an inherited defect in neutrophil oxidative burst as a result of mutations in one of the three genes, NCF1, NCF2, and CYBA, which respectively encode p47-phox, p67-phox, and p22-phox subunits of the NADPH oxidase complex.Objective: To investigate clinical and molecular characteristics of two unrelated Thai patients with AR-CGD.Methods: A Thai girl who suffered from pulmonary aspergillosis at the age of two months and another unrelated Thai boy presented with recurrent cutaneous abscesses caused by Chromobacterium violaceum since 30 months old, were investigated. The DHR assays revealed abnormalities in both patients but normal results in their mothers, consistent with the diagnosis of AR-CGD. PCR-sequencing of the entire coding regions of NCF1, NCF2, and CYBA was performed.Results: A homozygous c.75_76delGT mutation at the beginning of exon 2 of NCF1 was identified in both individuals. This mutation resulted in a frameshift with premature termination of p47-phox at codon 51 (p.Val25fsX51).Conclusion: The homozygous GT deletion in NCF1 may be a common mutation in Thai patients with AR-CGD. Unlike all other autosomal recessive disorders, AR-CGD caused by NCF1 mutations has a unique mutational pattern, in which there is only one mutation responsible for most patients regardless of their ethnic backgrounds.