Abstract
Hemangioblastomas (HBs) are classified as grade I tumors with uncertain origin according to the World Health Organization's classification system. HBs are characterized by rich mesenchymal cells and abundant capillaries. It has been shown that tumorigenesis of HBs depends on mutational inactivation of Von Hippel-Lindau (VHL) tumor suppressor gene. Therefore, the majority of patients will undergo VHL single gene test, and sequencing scheme is rarely used in clinic. In this study, we described a girl and her father successively found to have HBs within half a year. The results of next-generation sequencing (NGS) and Sanger sequencing analysis showed that both of them carried heterozygous mutation of RNF139 p.Q650R. This mutation was interpreted as Pathogenic variation based on the American College of Medical Genetics and Genomics (ACMG) guideline. Sanger sequencing was performed with other family members. No mutation on rs118184842 locus of RNF139 gene was found in the samples from the girl's mother, uncle and aunt. This report supports that the novel mutation of RNF139 p.Q650R probably serve as a key role in HBs progression.