Novel and recurrent genetic variants of VHL, SDHB, and RET genes in Chinese pheochromocytoma and paraganglioma patients

Chong Li; Jingyi Li; Chao Han; Ting Wang; Lixia Zhang; Zhifang Wang; Tingting Wang; Lijun Xu; Guangzhao Qi; Guijun Qin; Xialian Li; Lili Zheng

doi:10.3389/fgene.2023.959989

Novel and recurrent genetic variants of VHL, SDHB, and RET genes in Chinese pheochromocytoma and paraganglioma patients

Front Genet. 2023 Mar 3:14:959989. doi: 10.3389/fgene.2023.959989. eCollection 2023.

Authors

Chong Li¹, Jingyi Li², Chao Han³, Ting Wang³, Lixia Zhang¹, Zhifang Wang¹, Tingting Wang¹, Lijun Xu¹, Guangzhao Qi³, Guijun Qin¹, Xialian Li¹, Lili Zheng¹

Affiliations

¹ Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Department of Plastic Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
³ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Background: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors arising from chromaffin cells in the adrenal medulla and extra-adrenal ganglia, respectively. The study was aimed to investigate the clinical and genetic characteristics of 22 individuals from six families. Methods: The medical records of six PPGL probands who presented to our hospital between 2016 and 2021 were retrospectively studied. DNA isolated from the probands was analyzed using whole exome sequencing. The identified genetic variants were confirmed by Sanger sequencing and undergone bioinformatic analysis. Results: Six different genetic variants in the six probands were identified, respectively, of which three were novel. A novel von Hippel-Lindau (VHL) variant, c.602T>C (p.L201P), in exon 3 was found. Two novel genetic variants in SDHB (succinate dehydrogenases subunit B), c.423 + 1 G>T and c.662A>G (p.D221G), were identified. Two recurrent genetic variants of VHL, c.C284G (p.P95R) and c.558_560AGAdel (p.186Edel), and one in RET (ret proto-oncogene), c.1901G>A (p.C634Y), were also found. The ClinVar accession number for the present variants are SCV002028348, and SCV002028352 to SCV002028361. Conclusion: Genetic variants in VHL, SDHB and RET were identified in Chinese PPGL patients, which contributed to the knowledge of the genetic etiology and clinical outcome of these tumors.

Keywords: RET; SDHB; VHL; paraganglioma; pheochromocytoma.

Grants and funding

The study was supported by the grants from Young Investigators Foundation of The First Affiliated Hospital of Zhengzhou University (Grant No. YNQN2017125), Joint Projects of Medical Science and Technology Problem-Tackling Plan of Henan Province (Grant No. LHGJ20190270), Natural Science Foundation of Henan Province (Grant No. 212300410246).