46, XY Sex Development Defect due to a Novel Homozygous (splice site) c.673_1G>C Variation in the HSD17B3 Gene: Case Report.

The enzyme 17-β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) catalyzes the biosynthesis of testosterone from Δ4-androstenedione, and plays an important role in the final steps of androgen synthesis. 17β-HSD3 deficiency originates from mutations in the HSD17B gene, causing an autosomal recessive 46, XY sex developmental disorder (DSD). Patients with 46, XY karyotype can exhibit a wide phenotypic spectrum varying from complete external female genitalia to male genitalia with hypospadias. This study reports a case of 17β-HSD3 deficiency diagnosed in the infantile period who was later found to have a novel HSD17B3 gene variation. The 14-month old patient, who exhibited a female phenotype, presented with a bilateral lump in the inguinal area. Imaging revealed bilateral testicular gonads in the inguinal area. Hormonal evaluation showed low levels of basal and stimulated serum testosterone (T), a high level of androstenedione (A), and a low T/A ratio. Chromosomal analysis showed 46, XY karyotype. The patient's sequence analysis of the HSD17B3 gene revealed a c.673_1G>C homozygous class 2 (splice site) variation in intron 9. The father and mother were heterozygous carriers of the same variation. This variation has not been previously reported in the literature. In conclusion, a 46, XY DSD should be considered in patients with a female phenotype who exhibit gonad(s) in the inguinal area at an early age; in patients with insufficient testosterone synthesis and high levels of androstenedione, 17β-HSD3 should be considered, and molecular analysis should be done for a definitive diagnosis and subsequent genetic counseling.