Genetic changes in the FH gene cause vagal paraganglioma

Whole exome and transcriptome sequencing data for the report of a case of FH-mutated vagal paraganglioma. In this study, we reported a rare case of 41 years old woman with VPGL carrying a germline mutation in the FH gene. Based on whole-exome sequencing, a novel variant FH: p.S249R was identified; no mutations were found in other PPGL susceptibility genes. The loss of heterozygosity analysis revealed the loss of the wild-type allele of the FH gene in the tumor. The pathogenic effect of p.S249R mutation on FH activity was confirmed using immunohistochemistry of S-(2-succino)-cysteine (2SC). Somatic potentially deleterious variants were found in three genes, SLC7A7, ZNF225, and MED23, the last two of which encode transcriptional regulators that could impact gene expression deregulation and be involved in tumor development and progression. In addition, we have shown that FH-mutated VPGL is characterized by molecular phenotype different from SDHx-mutated PPGLs.