To explore the application of next-generation targeted nuclear genome sequencing in the diagnosis and treatment of patients with suspected disorders of sex development (DSD).

The data of 53 suspected patients with DSD were admitted from July 2017 to July 2020, and the peripheral blood DNA of the patients and their parents were collected. The next generation of targeted nuclear genome sequencing of DSD patients was carried out using a panel containing 141 targeted nuclear genomes, and the results were analyzed.

Among the 53 patients with suspected DSD, 21 cases of related chromosomal or gene variants were detected. Among them, 13 cases were pathogenic variants or likely pathogenic variants, 7 were novel variants, and 1 of uncertain significance. Two of the seven new variants were predicted as pathogenic variants, so the diagnosis rate was 28.3%(15/53). The positive rate was 39.6%(21/53), and the genes involved SRD5A2, CHD7, AR, NR5A1, NSMF, MAP3K1, MAMLD1, ANOS1, including 1 case 47, XXY DSD and ovotesticular DSD, and 20 cases 46, XY DSD, 20 of which were treated by surgery. 32 children had corresponding clinical symptoms, but no corresponding genetic variation was detected. 31 cases were treated with surgery.

Targeted next-generation nuclear genome sequencing improves the early diagnosis rate of suspected DSD patients, and the results can help for the choice of treatment.