Background: Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare, mostly benign tumors. Most of these tumors are sporadic but a significant percentage can be found as components of hereditary tumor syndromes caused by germline mutations of the VHL, RET, NF1, SDHD, SDHC, SDHB and the recently identified SDHAF2 genes. Germline mutations of these genes can be also found in several cases with apparently sporadic Pheo/PGL.
Aim: The aim of our study was to analyze the prevalence of germline mutations in patients with apparently sporadic Phaeo/PGL.
Materials and methods: Mutations analysis of the RET, VHL, SDHC, SDHB, SDHD and SDHAF2 genes were performed in 69 patients (27/42 male/female, age: 38.2 (1472) mean range, years) with apparently sporadic Pheo/PGL consecutively admitted for evaluation. Patients were clinically evaluated and genetic analysis was performed using PCR, direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) of the VHL gene.
Results: Of the 69 patients 14 patients (20.2%) had pathogenic germline mutation. Six patients had mutation of the RET protooncogen (Cys611Tyr, Cys634Tyr, Cys634Trp, Cys634Arg and in two unrelated cases Ser649Leu), five patients showed VHL gene (Pro63Leu, Arg79Gly, Tyr156Cys and in two unrelated patients Arg167Gln), one patient SDHD gene (c147148 insA) and two patients SDHB gene mutations (Cys243Tyr and Cys253Tyr). Of the 14 mutation carriers four patients (one with VHL and three with RET mutation) were older than 40 years at the time of diagnosis of Pheo/PGL.
Conclusion: The prevalence of disease-causing mutations among Hungarian patients with apparently sporadic Pheo/PGL is similar to those reported in the literature. However, Cys649Leu mutation of the RET gene classified as a mutation causing mild phenotype has not been previously associated with Pheo. Both Arg79Gly of the VHL gene and Cys243Tyr of the SDHB gene are novel disease-causing mutations. In addition, our results suggest that complex genetic testing is useful not only in younger but also in older cases.
30 Apr - 04 May 2011
European Society of Endocrinology