Intra-familial phenotypic heterogeneity and telomere abnormality in von Hippel-Lindau disease
Intra-familial phenotypic heterogeneity and telomere abnormality in von Hippel-Lindau disease
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.
Wang Jiangyi、Peng Xiang、Ning Xianghui、Peng Shuanghe、Li Teng、Cai Lin、Hong Baoan、Liu Shengjie、Zhou Jingcheng、Chen Cen、Ma Kaifang、Gong Kan
Department of Urology, Peking University First Hospital||Department of Urology, Fudan University Shanghai Cancer CenterDepartment of Urology, Peking University First Hospital||Department of Urology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Urology, Peking University First Hospital||Department of Urology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Urology, Peking University First Hospital||Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical UniversityDepartment of Urology, Peking University First Hospital||Department of Urology, Guangdong General Hospital, Guangdong Academy of Medical SciencesDepartment of Urology, Peking University First HospitalDepartment of Urology, Peking University First HospitalDepartment of Urology, Peking University First Hospital||Department of Urology, Beijing HospitalDepartment of Urology, Peking University First HospitalSchool of Statistics, Renmin UniversityDepartment of Urology, Peking University First HospitalDepartment of Urology, Peking University First Hospital
医学研究方法肿瘤学基础医学
von Hippel-Lindau diseasephenotypic heterogeneitygenetic anticipationbirth order effecttelomere length
Wang Jiangyi,Peng Xiang,Ning Xianghui,Peng Shuanghe,Li Teng,Cai Lin,Hong Baoan,Liu Shengjie,Zhou Jingcheng,Chen Cen,Ma Kaifang,Gong Kan.Intra-familial phenotypic heterogeneity and telomere abnormality in von Hippel-Lindau disease[EB/OL].(2025-03-28)[2025-08-07].https://www.biorxiv.org/content/10.1101/526913.点此复制
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