Ovarian juvenile granulosa cell tumors with Ollier's disease in children with IDH1 gene somatic mutation

Front Endocrinol (Lausanne). 2023 May 30:14:1093273. doi: 10.3389/fendo.2023.1093273. eCollection 2023.

Abstract

Objective: The aim of this study was to explore the symptoms, treatment, and pathogenesis of ovarian juvenile granulosa cell tumors with Ollier's disease in children.

Methods: From October 2019 to October 2020, clinical data were retrospectively analyzed for one case of ovarian juvenile granulosa cell tumors with Ollier's disease. Whole-exome sequencing and Sanger sequencing were used to detect gene mutation in ovarian tumor and chondroma tissue. NADP-dependent isocitrate dehydrogenase-1 (IDH1) and S6 ribosomal protein expression levels in cells transfected with wild-type or mutant plasmid were analyzed by Western blot.

Results: The 4-year-old female showed multiple skeletal deformities, bilateral breast development with chromatosis, and vulvar discharge. Sex hormone assay suggested that estradiol and prolactin were elevated, and the x-ray of limbs suggested enchondroma. Pelvic ultrasound and abdominal CT revealed a right ovarian solid mass. Pathologic examination of the right ovarian solid mass showed a juvenile granulosa cell type. A c.394C>T (p. Arg132Cys) mutation of the IDH1 gene was detected in both the ovarian juvenile granulosa cell tumors and enchondroma. Transfection of HeLa cells with either WT or Mut plasmid caused 4.46- or 3.77-fold overexpression of IDH1 gene compared to non-transfected control cells, respectively. R132C mutation inhibited the phosphorylation of S6 ribosomal protein, which is central to the mTOR pathway. Postoperatively, estradiol and prolactin levels fell to values normal for her age and bilateral breast gradual retraction.

Conclusion: The incidence of ovarian juvenile granulosa cell tumors with Ollier's disease in children may be caused by generalized mesodermal dysplasia; IDH1 gene mutation may play a facilitated role in this process. Surgical operation is the main treatment. We suggest that patients with ovarian juvenile granulosa cell tumors and Ollier's disease should undergo regular investigation.

Keywords: IDH1; Ollier’s disease; children; gene; juvenile granulosa cell tumors; ovarian.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Enchondromatosis* / genetics
  • Estradiol
  • Female
  • Granulosa Cell Tumor* / genetics
  • Granulosa Cell Tumor* / pathology
  • HeLa Cells
  • Humans
  • Isocitrate Dehydrogenase
  • Prolactin
  • Retrospective Studies
  • Ribosomal Proteins

Substances

  • Prolactin
  • Ribosomal Proteins
  • Estradiol
  • IDH1 protein, human
  • Isocitrate Dehydrogenase

Supplementary concepts

  • Granulosa cell tumor of the ovary

Grants and funding

This work was supported by the Wu Jieping Medical Foundation special fund for clinical research (320.6750.2020-06-86), the National Natural Science Foundation of China (No. 81971453), the Shenzhen Fundamental Research Program, China (No. JCYJ20200109150429414), the Shenzhen Science and Technology Program, China (No. RCYX20200714114705073 and No. KQTD20190929172749226), the Sanming Project of Medicine in Shenzhen, China (No. SZSM201612083), the HKU-SZH Fund for Shenzhen Key Medical Discipline-Reproductive medicine (No. SZXK2020089), and the Shenzhen Key Laboratory of Metabolic Health (Grant No. ZDSYS20210427152400001).