Mutation Frequency in Main Susceptibility Genes Among Patients With Head and Neck Paragangliomas

Abstract

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors that have a high degree of heritability and are predominantly associated with mutations in ten genes, such as <i>SDHx, SDHAF2, VHL, RET, NF1, TMEM127, MAX, FH, MEN2</i>, and <i>SLC25A11</i>. Elucidating the mutation prevalence is crucial for the development of genetic testing. In this study, we identified pathogenic/likely pathogenic variants in the main susceptibility genes in 102 Russian patients with HNPGLs (82 carotid and 23 vagal paragangliomas) using whole exome sequencing. Pathogenic/likely pathogenic variants were detected in 43% (44/102) of patients. We identified the following variant distribution of the tested genes: <i>SDHA</i> (1%), <i>SDHB</i> (10%), <i>SDHC</i> (5%), <i>SDHD</i> (24.5%), and <i>RET</i> (5%). <i>SDHD</i> variants were observed in the majority of the patients with bilateral/multiple paragangliomas. Thus, among Russian patients with HNPGLs the most frequently mutated gene was <i>SDHD</i> followed by <i>SDHB, SDHC, RET</i>, and <i>SDHA</i>.