Abstract
The present study describes the successful application of next-generation sequencing (NGS) in the clinical diagnosis, pathogenic gene identification, treatment and pre-natal diagnosis in a pedigree with chronic granulomatosis disease (CGD). A 36-day-old infant, born to non-consanguineous Chinese parents, was admitted to hospital due to a neck lump for 10 days. A blood sample was collected for NGS to identify the molecular etiology. Sanger sequencing was performed for the patient and his relatives, including the parents. Amniotic fluid exfoliative cells from the mother were collected for pre-natal diagnosis at week 16 of a subsequent pregnancy. A novel c.1520_1521del, p.Lys508Aspfs*10 (NM_000397) variant in the cytochrome b-245 β chain (CYBB) gene was identified in the proband, while the mother and the proband's 1-year-old sister were heterozygotes at this site. Karyotype analysis indicated that the fetus of the subsequent pregnancy was male. Sanger sequencing of amniotic cell DNA revealed that the fetus did not have the CYBB abnormality at the site. The results of the present study suggest that the variant in the CYBB gene was the cause of CGD in this pedigree and that pre-natal diagnosis using NGS is an effective method for providing genetic counseling to pedigrees with CGD.