Germline mutations in the VHL gene associated with 3 different renal lesions in a Chinese von Hippel-Lindau disease family |
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| Authors: | Ping Yuan Qipeng Sun Hao Liang Wenjun Wang Ling Li Ye Wang |
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| Institution: | 1. Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Obstetrics and Gynecology, IVF Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;2. Department of Urology, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;3. Center for Quantitative Biology, Peking University, Beijing, China;4. BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, and Peking-Tsinghua Center for Life Sciences at College of Chemistry and Molecular Engineering, Peking University, Beijing, China;5. Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-sen University, Guangzhou, China |
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| Abstract: | Von Hippel–Lindau (VHL) disease is a rare autosomal dominant inherited cancer syndrome that is characterized by hemangioblastomas in the central nervous system and retina, renal cell carcinoma and cysts, pancreatic tumors and cysts, and pheochromocytoma. The underlying gene in this disease is the VHL tumor suppressor gene. We characterized a family with 2 affected siblings. The brother and sister displayed VHL type 2B and type 2A features, respectively. Renal lesions in the brother exhibited 3 different phenotypes, including simple renal cysts, multilocular cystic renal cell carcinoma and clear cell renal cell carcinoma. The phenotypes of the 3 concurrent renal lesions were first reported in this study. Mutation detection of the VHL gene revealed 2 recurrent mutations, namely c.256C>T (p.P86S) and c.340 + 5G > C. The former was predicted to be deleterious and to destabilize the hydrophobic core and lead to VHL dysfunction; however, the latter was predicted to be a benign variant. Our findings provided new data for the genotype-phenotype of VHL diseases and elucidated the pathogenic mechanism with in silico analysis. |
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| Keywords: | Clear cell renal cell carcinoma multilocular cystic renal cell carcinoma mutation von Hippel–Lindau disease VHL |
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