Cocchetti Carlotta, Baldinotti Fulvia, Romani Alessia, Ristori Jiska, Mazzoli Francesca, Vignozzi Linda, Maggi Mario, Fisher Alessandra Daphne
Andrology, Women's Endocrinology and Gender Incongruence Unit, Florence University Hospital, Florence, Italy.
Laboratory of Molecular genetics, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Sex Med. 2022 Aug;10(4):100522. doi: 10.1016/j.esxm.2022.100522. Epub 2022 May 17.
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.
3型17β-羟基类固醇脱氢酶（17β-HSD3）缺乏症是一种罕见的常染色体隐性46,XY性发育异常（DSD），由HSD17B3基因的致病变异引起，该变异导致胎儿睾丸中Δ4-雄烯二酮转化为睾酮的能力缺失或降低。
本研究旨在介绍一名成年时被诊断为17β-HSD3缺乏症的意大利患者的临床和遗传特征。该患者自幼被当作女性抚养，并接受了早期手术干预以矫正男性化生殖器，这导致了严重的性困扰。
在转诊时，对患者的基因组DNA进行了针对DSD的20基因新一代测序定制面板检测。
在HSD17B3基因中鉴定出一种新的复合杂合突变，检测到一个新变异（c.257_265delAGGCCATTG，p.）。结论：呈现了导致17β-HSD3缺乏症的新基因型。此外，患者的临床病史强调了让这些个体积极参与决策过程的重要性，在患者无法给出充分知情同意时避免进行手术干预。科切蒂C、巴尔迪诺蒂F、罗马尼A等。在一名46,XY性发育异常患者中鉴定出HSD17B3基因的一种新型复合杂合突变。性医学2022；10：100522。
