| Autor: |
Sheng-Jie, Liu, Jiang-Yi, Wang, Shuang-He, Peng, Teng, Li, Xiang-Hui, Ning, Bao-An, Hong, Jia-Yuan, Liu, Peng-Jie, Wu, Bo-Wen, Zhou, Jing-Cheng, Zhou, Nie-Nie, Qi, Xiang, Peng, Jiu-Feng, Zhang, Kai-Fang, Ma, Lin, Cai, Kan, Gong |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Genetics in medicine : official journal of the American College of Medical Genetics. 20(10) |
| ISSN: |
1530-0366 |
| Popis: |
Von Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype-phenotype correlation based on alterations in VHL protein (pVHL).VHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared.Missense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p 0.001) and lower risks of central nervous system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR = 0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p 0.001) than those in the combined HM and TR (HMTR) group. Moreover, nHM mutations were independently associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific survival (HR = 0.129, p = 0.005) than HMTR mutations.The modified genotype-phenotype correlation links VHL gene mutation, substrate binding site, and phenotypic diversity (penetrance and survival), and provides more accurate information for genetic counseling and pathogenesis studies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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