In addition to adrenal insufficiency, gonadal function is also impaired in patients with 3β-HSD2 deficiency. Affected male individuals encounter incomplete virilization, with clinical signs ranging from mild hypospadias to genital ambiguity due to impaired testosterone biosynthesis. 46XX individuals have normal female genitalia or show moderate signs of virilization of the external genitalia with clitoromegaly. These features are linked to an overproduction of DHEA by the foetal adrenals, which in turn can be converted to testosterone by extra-adrenal 3βHSD1 [10,11,12,13,14,15,16]. Herewith, we report the presence of 3β-HSD2 deficiency in two siblings who attended the Pediatric Endocrinology Centre of the Regina Margherita Children’s Hospital of Turin and who presented with compound heterozygote for one novel missense variant and a splicing variant in the HSD3B2 gene. We performed in silico analysis to assess the effects of the missense variant on enzyme activity and the effect of the intronic variant on splicing. 2.1. Patients, Clinical Presentation and Hormonal Analysis.
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