AUTHOR=Snezhkina Anastasiya V. , Fedorova Maria S. , Pavlov Vladislav S. , Kalinin Dmitry V. , Golovyuk Alexander L. , Pudova Elena A. , Guvatova Zulfiya G. , Melnikova Nataliya V. , Dmitriev Alexey A. , Razmakhaev George S. , Poloznikov Andrey A. , Alekseeva Galina S. , Kaprin Andrey D. , Krasnov George S. , Kudryavtseva Anna V. 

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

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.614908

DOI=10.3389/fgene.2020.614908

ISSN=1664-8021

ABSTRACT=<p>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 <italic>SDHx, SDHAF2, VHL, RET, NF1, TMEM127, MAX, FH, MEN2</italic>, and <italic>SLC25A11</italic>. 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: <italic>SDHA</italic> (1%), <italic>SDHB</italic> (10%), <italic>SDHC</italic> (5%), <italic>SDHD</italic> (24.5%), and <italic>RET</italic> (5%). <italic>SDHD</italic> 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 <italic>SDHD</italic> followed by <italic>SDHB, SDHC, RET</italic>, and <italic>SDHA</italic>.</p>