Introduction: According to recent literature, somatic mutations in the ubiquitin-specific protease 8 (USP8) gene are the most common changes in patients with Cushing's disease (CD). Data on the frequency of these mutations in the paediatric population are limited. The aim of the presented study was to determine the frequency of the USP8 gene mutations in a group of paediatric patients with CD treated at the Children's Memorial Health Institute (CMHI).
Material and methods: Eighteen patients (nine females) with CD were treated at CMHI, Warsaw, Poland between 1993 and 2019. All patients underwent transsphenoidal surgery (TSS) as a primary treatment for CD. The average age of all patients at TSS was 13.10 years (5.42-17.25). DNA was extracted from formalin-fixed paraffin-embedded resected tumour tissue. Sanger sequencing was performed on DNA sequence corresponding to the exon 14 of USP8 gene.
Results: The mean age at diagnosis of CD was 13.08 years, and the average duration of symptoms before diagnosis was 2.96 years. All patients were operated at CMHI by the same neurosurgeon. Fifteen out of 18 patients (83.33%) had initial biochemical remission after a single TSS procedure (post-operative serum cortisol < 1.8 μg/dL). The result of genetic testing was negative for all samples at the hotspot area of the USP8 gene.
Conclusion: The current retrospective study demonstrates that mutations in the USP8 gene may not be as common a cause of paediatric Cushing's disease, as previously reported.
Keywords: Cushing’s disease; USP8 gene mutations; molecular background; transsphenoidal surgery.