A Novel Compound Heterozygous Mutation of HSD17B3 Gene Identified in a Patient With 46,XY Difference of Sexual Development

Deficiency of the 17β-hydroxysteroid dehydrogenase type 3 (17 β-HSD3) is a rare autosomal recessive 46,XY Difference of sex development (DSD), resulting from pathogenetic variants in the HSD17B3 gene, which lead to absent or reduced ability to convert Δ4-androstenedione to testosterone in the fetal testes.

This study aimed to present the clinical and genetic characteristics of an Italian patient receiving a diagnosis of 17 β-HSD3 deficiency in adulthood. The patient was raised as female and underwent early surgical interventions to correct virilized genitalia, leading to a significant sexual distress.

At the time of the referral, a 20-gene Next Generation Sequencing custom-panel for DSD was performed on patient's genomic DNA.

A novel compound heterozygous mutation in HSD17B3 gene was identified, detecting a new variant (c.257_265delAGGCCATTG, p.) CONCLUSION: Novel genotype causing 17 β-HSD3 deficiency is presented. Furthermore, the patient's clinical history stresses the importance to actively involve these individuals in the decision-making process avoiding surgical intervention when the patient is not able to give fully informed consent. Cocchetti C, Baldinotti F, Romani A, et al. A Novel Compound Heterozygous Mutation of HSD17B3 Gene Identified in a Patient With 46,XY Difference of Sexual Development. Sex Med 2022;10:100522.