Frontiers in Genetics (Sep 2019)
Frequent Mutations of VHL Gene and the Clinical Phenotypes in the Largest Chinese Cohort With Von Hippel–Lindau Disease
- Baoan Hong,
- Baoan Hong,
- Baoan Hong,
- Baoan Hong,
- Baoan Hong,
- Baoan Hong,
- Kaifang Ma,
- Kaifang Ma,
- Kaifang Ma,
- Kaifang Ma,
- Jingcheng Zhou,
- Jingcheng Zhou,
- Jingcheng Zhou,
- Jingcheng Zhou,
- Jiufeng Zhang,
- Jiufeng Zhang,
- Jiufeng Zhang,
- Jiufeng Zhang,
- Jiangyi Wang,
- Jiangyi Wang,
- Jiangyi Wang,
- Jiangyi Wang,
- Shengjie Liu,
- Shengjie Liu,
- Shengjie Liu,
- Shengjie Liu,
- Zhongyuan Zhang,
- Zhongyuan Zhang,
- Zhongyuan Zhang,
- Zhongyuan Zhang,
- Lin Cai,
- Lin Cai,
- Lin Cai,
- Lin Cai,
- Ning Zhang,
- Ning Zhang,
- Kan Gong,
- Kan Gong,
- Kan Gong,
- Kan Gong
Affiliations
- Baoan Hong
- Department of Urology, Peking University First Hospital, Beijing, China
- Baoan Hong
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Baoan Hong
- Institute of Urology, Peking University, Beijing, China
- Baoan Hong
- National Urological Cancer Center, Beijing, China
- Baoan Hong
- Department of Urology, Beijing Cancer Hospital, Beijing, China
- Baoan Hong
- Beijing Institute for Cancer Research, Beijing, China
- Kaifang Ma
- Department of Urology, Peking University First Hospital, Beijing, China
- Kaifang Ma
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Kaifang Ma
- Institute of Urology, Peking University, Beijing, China
- Kaifang Ma
- National Urological Cancer Center, Beijing, China
- Jingcheng Zhou
- Department of Urology, Peking University First Hospital, Beijing, China
- Jingcheng Zhou
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Jingcheng Zhou
- Institute of Urology, Peking University, Beijing, China
- Jingcheng Zhou
- National Urological Cancer Center, Beijing, China
- Jiufeng Zhang
- Department of Urology, Peking University First Hospital, Beijing, China
- Jiufeng Zhang
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Jiufeng Zhang
- Institute of Urology, Peking University, Beijing, China
- Jiufeng Zhang
- National Urological Cancer Center, Beijing, China
- Jiangyi Wang
- Department of Urology, Peking University First Hospital, Beijing, China
- Jiangyi Wang
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Jiangyi Wang
- Institute of Urology, Peking University, Beijing, China
- Jiangyi Wang
- National Urological Cancer Center, Beijing, China
- Shengjie Liu
- Department of Urology, Peking University First Hospital, Beijing, China
- Shengjie Liu
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Shengjie Liu
- Institute of Urology, Peking University, Beijing, China
- Shengjie Liu
- National Urological Cancer Center, Beijing, China
- Zhongyuan Zhang
- Department of Urology, Peking University First Hospital, Beijing, China
- Zhongyuan Zhang
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Zhongyuan Zhang
- Institute of Urology, Peking University, Beijing, China
- Zhongyuan Zhang
- National Urological Cancer Center, Beijing, China
- Lin Cai
- Department of Urology, Peking University First Hospital, Beijing, China
- Lin Cai
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Lin Cai
- Institute of Urology, Peking University, Beijing, China
- Lin Cai
- National Urological Cancer Center, Beijing, China
- Ning Zhang
- Department of Urology, Beijing Cancer Hospital, Beijing, China
- Ning Zhang
- Beijing Institute for Cancer Research, Beijing, China
- Kan Gong
- Department of Urology, Peking University First Hospital, Beijing, China
- Kan Gong
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
- Kan Gong
- Institute of Urology, Peking University, Beijing, China
- Kan Gong
- National Urological Cancer Center, Beijing, China
- DOI
- https://doi.org/10.3389/fgene.2019.00867
- Journal volume & issue
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Vol. 10
Abstract
Von Hippel–Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age at onset for VHL-associated susceptible organs were calculated and compared. The overall survival of VHL patients was described with Kaplan–Meier curves. Among the 19 frequent germline mutations, there were four hotspot mutation sites (194, 481, 499, and 500). Missense mutations were the most common types of mutations (70.0%) followed by nonsense mutations (20.0%) and splicing mutations (10.0%). Due to the diversity of these mutations, the penetrance for each organ and the age at onset are distinct. Even in cases of similar mutations, variance in the penetrance and age at onset was observed. The mean age at death for the patients in this cohort was 42.4 ± 13.5 years, and variability was observed in the Kaplan–Meier curves. We present a precise summary of the phenotypes for the frequent VHL mutations in the largest Chinese VHL cohort, which provides valuable strategies for genetic counseling and clinical surveillance of VHL individuals.
Keywords
