ESPE Abstracts

We report a large family with several cases of 46 XY and a new mutation in the 17-β-HSD3 gene.The proposita was an 11-year-old girl and the first child of a consanguineous family. She was born by cesarean section with a height of 52 cm and a weight of 4200 grams. The external genitalia were completely female and had a short vaginal pouch. She had palpable gonads in her inguinal area and underwent bilateral gonadectomy at the age of two. Other physical examinations were normal. At age 10, she was referred to our clinic for more evaluation at the Hospital for the Sick Children in Qazvin, Iran. In pelvic sonography, uterine and ovarian were not seen. Her karyotype was 46, XY and her LH and FSH levels were elevated.We realized that three of the patient's aunts and one of the mother's aunts had the same phenotype; their karyotype was 46, XY and had symptoms of virilization because they had not had an orchiectomy before puberty. Our adult patients accepted female gender identity, married, and had female gender behavior but lacked fertility. Using whole exome sequencing, we identified a novel homozygous missense variation (c.731T>A, p. Ile244Lys) in HSD17B3 gene. This alteration changes Isoleucine to Lysine in exon 10. This variation – which has not been reported before – is predicted to be a variant of unknown significance (VUS) based on computational analysis.