Case Report: First report of a novel homozygous nonsense mutation in the CYBA gene causing chronic granulomatous disease.

OBJECTIVE

To investigate the etiology of recurrent severe pneumonia and pleural effusion in a pediatric patient through pathogenic gene testing and bioinformatics analysis.

METHODS

Clinical characteristics and laboratory findings were retrospectively reviewed. Peripheral blood samples were collected from the patient and both parents. Genomic DNA was extracted and subjected to trio whole-exome sequencing (WES) using high-throughput sequencing technology. Sanger sequencing was used to validate suspected pathogenic variants.

RESULTS

Whole-exome sequencing revealed a homozygous variant c.427C>T (p.Q143*) in exon 6 of the CYBA gene, inherited from both parents. This variant has not been previously reported in the literature. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, c.427C>T(p.Q143*) was assessed as a likely pathogenic variant (PVS1_Strong+PM2_Supporting+PM3_Supporting). This variant is associated with autosomal recessive chronic granulomatous disease type 4(A22° CGD).

CONCLUSION

This study identified a novel CYBA gene variant in a pediatric patient with recurrent severe pneumonia and pleural effusion, expanding the spectrum of pathogenic variants in this gene and providing evidence for clinical diagnosis and genetic counseling.