Background: Disorders of sex development (DSD) vary phenotypically and are caused by a number of genetic etiologies. Although several genetic abnormalities have been discovered through genetic analyses, the underlying genetic causes of 46, XY DSD remain unknown in most of the cases
Aim: To identify genetic defects in patients with 46,XY DSD.
Material and Methods: A total 76 DSD patients included in the study, 22 of these patients who were screened and did not carry mutations for SRD5A2 and AR genes and 54 patients suspected to have gonadal dysgenesis or androgen synthesis defects. 31 DSD associated genes were sequenced using in-house-designed next generation sequencing (NGS) targeted panel-gene and analyzed for gross deletion/duplication with MLPA (P185 and P334).
Results: 12 previously described and 22 suspected rare variants are identified in 15 different genes within a total of 32 cases, leading to a diagnostic rate to 40.5%. Highest rate of causative variants was identified in HSD17B3 (11.1%) which was followed by, NR5A1, LHCGR, DHH, ZFMP2, SR5A2, SOX9, WT1, POR, HOXA4, AMHR2, CYP5A, AR, MAP3K1 and GATA4. Genetic results led to a change of initial clinical diagnosis of some patients with androgen synthesis and androgen action groups and these patients were reclassified as disorder of gonadal dysgenesis.
Conclusion: Genetic analyses following clinical and hormonal evaluation is essential for the definitive diagnosis, management and counseling of patients and families with 46,XY DSD with a great phenotypic and genetic heterogeneity. NGS targeted panel gene seems to be a powerful tool to detect associated variants of DSD.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology