Endocrine Abstracts

Background: The CYP17A1 gene encodes the enzyme cytochrome P450c17, which plays a crucial role in steroidogenesis. Biallelic pathogenic variants in the CYP17A1 gene are responsible for autosomal recessive combined or partial 17α-hydroxylase/17,20-lyase deficiency (17-OHD), characterized by cortisol and sex steroid deficiencies, as well as excessive mineralocorticoid production.

Aim: This study investigated three patients with 46,XY DSD, who presented with hypergonadotropic hypogonadism and hypertension that developed later in life.

Methods: This study included three female reared patients with the complaint of primary amenorrhea. All patients were subjected to full history taking, pedigree analysis, thorough clinical examination, pelvic imaging and assessment of hormonal profiles. Patients underwent karyotyping, laparoscopy with gonadal biopsy, and histopathological examination. Exome sequencing (ES) was performed.

Results: Exome sequencing identified two homozygous variants in the CYP17A1 gene. Computational and in silico analyses indicated that both variants, p.Ser379Phe and p.Trp406Ter, are predicted to result in the loss of enzymatic function.

Conclusions: Patients with 17-hydroxylase deficiency (17-OHD) typically exhibit a full range of symptoms associated with the disorder. Molecular analysis is crucial for confirming the diagnosis in patients with 17-OHD, as the hormonal and clinical features can be quite challenging to interpret. The limited availability of advanced steroid profiling techniques, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), poses additional diagnostic challenges, highlighting the need for improved access to these technologies. The detection of novel homozygous variants expands the genotypic spectrum and underscores the importance of studying additional patients while considering the clinical and hormonal criteria for diagnosing 17-OHD.