Intra-Familial Phenotypic Heterogeneity and Telomere Abnormality in von Hippel- Lindau Disease: Implications for Personalized Surveillance Plan and Pathogenesis of VHL-Associated Tumors

In conclusion, this study provides definitive evidence of intra-familiar phenotypic variety in VHL families including genetic anticipation and birth order effect. Clinicians should take the position in the family tree into consideration when they are making surveillance plan for VHL patients. Although we confirm that telomere shortening plays a role in the molecular mechanism of phenotypic heterogeneity within VHL families, the detailed effect of inactivated VHL protein on genomic instability remains unclear, and the explanation for birth order effect needs further exploration. Ethics Statement This study was carried out in accordance with the recommendations of “the Medical Ethics Committee of Peking University First Hospital (Beijing, China)” with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the “Medical Ethics Committee of Peking University First Hospital (Beijing, China).” Author Contributions KG developed the hypothesis and secured the funding. JW wrote the first draft of the manuscript. CC, XN, and XP carried out the statistical analyses. SP, BH, and TL dealt with figures and tables. SL, JZ, and KM performed the data collection. LC revised the manuscript. All authors critically commented on and approved the final version of the manuscript. Funding This work was supported by the National Natural Science Foundation of Chi...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research