Frontiers in Genetics (Apr 2019)
Intra-Familial Phenotypic Heterogeneity and Telomere Abnormality in von Hippel- Lindau Disease: Implications for Personalized Surveillance Plan and Pathogenesis of VHL-Associated Tumors
- Jiangyi Wang,
- Jiangyi Wang,
- Jiangyi Wang,
- Jiangyi Wang,
- Jiangyi Wang,
- Xiang Peng,
- Xiang Peng,
- Xiang Peng,
- Xiang Peng,
- Cen Chen,
- Xianghui Ning,
- Xianghui Ning,
- Xianghui Ning,
- Xianghui Ning,
- Shuanghe Peng,
- Shuanghe Peng,
- Shuanghe Peng,
- Shuanghe Peng,
- Teng Li,
- Teng Li,
- Teng Li,
- Teng Li,
- Shengjie Liu,
- Shengjie Liu,
- Shengjie Liu,
- Shengjie Liu,
- Baoan Hong,
- Baoan Hong,
- Baoan Hong,
- Jingcheng Zhou,
- Jingcheng Zhou,
- Jingcheng Zhou,
- Kaifang Ma,
- Kaifang Ma,
- Kaifang Ma,
- Lin Cai,
- Lin Cai,
- Lin Cai,
- Kan Gong,
- Kan Gong,
- Kan Gong
Affiliations
- Jiangyi Wang
- Department of Urology, Peking University First Hospital, Beijing, China
- Jiangyi Wang
- Institute of Urology, Peking University, Beijing, China
- Jiangyi Wang
- National Urological Cancer Center, Beijing, China
- Jiangyi Wang
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China
- Jiangyi Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Xiang Peng
- Department of Urology, Peking University First Hospital, Beijing, China
- Xiang Peng
- Institute of Urology, Peking University, Beijing, China
- Xiang Peng
- National Urological Cancer Center, Beijing, China
- Xiang Peng
- Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Cen Chen
- School of Statistics, Renmin University, Beijing, China
- Xianghui Ning
- Department of Urology, Peking University First Hospital, Beijing, China
- Xianghui Ning
- Institute of Urology, Peking University, Beijing, China
- Xianghui Ning
- National Urological Cancer Center, Beijing, China
- Xianghui Ning
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Shuanghe Peng
- Department of Urology, Peking University First Hospital, Beijing, China
- Shuanghe Peng
- Institute of Urology, Peking University, Beijing, China
- Shuanghe Peng
- National Urological Cancer Center, Beijing, China
- Shuanghe Peng
- Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China
- Teng Li
- Department of Urology, Peking University First Hospital, Beijing, China
- Teng Li
- Institute of Urology, Peking University, Beijing, China
- Teng Li
- National Urological Cancer Center, Beijing, China
- Teng Li
- 0Department of Urology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shengjie Liu
- Department of Urology, Peking University First Hospital, Beijing, China
- Shengjie Liu
- Institute of Urology, Peking University, Beijing, China
- Shengjie Liu
- National Urological Cancer Center, Beijing, China
- Shengjie Liu
- 1Department of Urology, Beijing Hospital, Beijing, China
- Baoan Hong
- Department of Urology, Peking University First Hospital, Beijing, China
- Baoan Hong
- Institute of Urology, Peking University, Beijing, China
- Baoan Hong
- National Urological Cancer Center, Beijing, China
- Jingcheng Zhou
- Department of Urology, Peking University First Hospital, Beijing, China
- Jingcheng Zhou
- Institute of Urology, Peking University, Beijing, China
- Jingcheng Zhou
- National Urological Cancer Center, Beijing, China
- Kaifang Ma
- Department of Urology, Peking University First Hospital, Beijing, China
- Kaifang Ma
- Institute of Urology, Peking University, Beijing, China
- Kaifang Ma
- National Urological Cancer Center, Beijing, China
- Lin Cai
- Department of Urology, Peking University First Hospital, Beijing, China
- Lin Cai
- Institute of Urology, Peking University, Beijing, China
- Lin Cai
- National Urological Cancer Center, Beijing, China
- Kan Gong
- Department of Urology, 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.2019.00358
- Journal volume & issue
-
Vol. 10
Abstract
von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome with poor survival. The current recommendations have proposed uniform surveillance strategies for all patients, neglecting the obvious phenotypic varieties. In this study, we aim to confirm the phenotypic heterogeneity in VHL disease and the underlying mechanism. A total of 151 parent-child pairs were enrolled for genetic anticipation analysis, and 77 sibling pairs for birth order effect analysis. Four statistical methods were used to compare the onset age of patients among different generations and different birth orders. The results showed that the average onset age was 18.9 years earlier in children than in their parents, which was statistically significant in all of the four statistical methods. Furthermore, the first-born siblings were affected 8.3 years later than the other ones among the maternal patients. Telomere shortening was confirmed to be associated with genetic anticipation in VHL families, while it failed to explain the birth order effect. Moreover, no significant difference was observed for overall survival between parents and children (p = 0.834) and between first-born patients and the other siblings (p = 0.390). This study provides definitive evidence and possible mechanisms of intra-familial phenotypic heterogeneity in VHL families, which is helpful to the update of surveillance guidelines.
Keywords
- von Hippel-Lindau disease
- phenotypic heterogeneity
- genetic anticipation
- birth order effect
- telomere length
