ESPE Abstracts (2018) 89 P-P1-219

Evaluation of Genetic Etiology in Patients with 46,XY Disorders of Sex Development: One Center Experience

Agharza Aghayeva, Guven Toksoya, Sukran Poyrazoglub, Birsen Karamana, Sahin Avcia, Melek Yildizb, Zehra Yavas Abalib, Umut Altunoglua, Firdevs Basb, Feyza Darendelilerb, Seher Basarana & Oya Uygunera


aIstanbul Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey; bIstanbul Faculty of Medicine, Pediatric Endocrinology Unit, Istanbul, Turkey


Background: Disorders of sex development (DSD) are a heterogeneous group of disorders related to sex determination and differentiation. Although several genetic abnormalities have been discovered through genetic analyses, the underlying genetic causes of 30–40% of the 46,XY DSD cases are not yet known.

Aim: To identify genetic defects in patients with 46,XY DSD.

Material and methods: Seventy-six patients with 46,XY DSD were studied. As a first step 56 patients suspected to have androgen insensitivity syndrome and 5alfa reductase deficiency according to their hormonal results are screened for SRD5A2 and AR gene mutations via Sanger sequencing. Twenty two patients who do not carry mutations in these genes and 20 patients suspected to have gonadal dysgenesis or androgen synthesis defects are enrolled into the next step and 31 DSD associated genes are sequenced using in-house-designed next generation sequencing (NGS) targeted gene panel and analyzed for gross deletion/duplication with MLPA.

Results: In the first group, SRD5A2 and AR gene mutations are detected 60.7% of cases. In the second group, seven previously described and 15 suspected rare variants are identified in 10 different genes within a total 19 cases, leading to our diagnostic rate to 45.2% for the second group. Highest rate of mutation is identified in HSD17B3 gene (16.7%) which is followed by mutations in DHH, NR5A1, LHCGR, POR, HOXA4, WT1, AR, ZFMP2 and MAP3K1 genes.

Conclusion: Genetic analyses following clinical and hormonal evaluation is essential for the management of patients with 46,XY DSD with a great phenotypic and genetic heterogeneity. NGS targeted gene panel seems powerful tool to detection mutations in DSD.