Risk factors for survival in patients with von Hippel-Lindau disease

Wang, J.Y.; Liu, S.J.; Hong, Bo; Zhou, Jianfeng; Ma, Kaplan; Gong, Kai

doi:10.1016/s1569-9056(18)31988-2

Cited by 4 publications

(6 citation statements)

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“…Furthermore, the median survival age in our cohort was 62 years old, in accordance with our previous analysis27 (figure 2B). Men seemed to have a shorter median survival than women (60 years vs 69 years), but the p value was 0.058 (figure 2C).…”

Section: Resultssupporting

confidence: 91%

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Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study

Xie

Ma²,

Zhang³

et al. 2020

J Med Genet

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BackgroundVon Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome resulting from mutations in the VHL gene lineage, and its prognosis is generally poor. This study aimed to provide a more valuable genotype–phenotype correlation based on the Elongin C binding site in VHL disease.MethodsThis study included 553 patients (194 families) who were diagnosed with VHL disease in our centre from September 2010 to February 2019. According to the type of gene mutation, the patients were divided into the Elongin C binding site missense mutation (EM) group, the non-Elongin C binding site missense mutation (nEM) group and the truncation mutation (TR) group. We analysed and compared the age-related tumour risk and prognosis of the three groups.ResultsA total of 14 new intragenic mutations were found in this cohort. The age-related risk of central nervous system haemangioblastoma (CHB) and pancreatic tumour in the EM group was lower than in the combined nEM-TR group, while the corresponding risk of pheochromocytoma (PHEO) was higher. Additionally, the prognoses of EM and nEM-TR were analysed. The median survival period in the EM group was longer than that in the nEM-TR group, and both the total survival and the CHB-specific survival of the EM group were better than those of the nEM-TR group.ConclusionIn conclusion, our study demonstrated that the EM was an independent risk factor for PHEO. The EM is also an independent protective factor for CHB age-related risk, overall survival and CHB-specific survival in VHL disease. This modified genotype–phenotype correlation integrates gene mutation, the Elongin B binding site, and phenotypic diversity and provides a reference for clinical diagnosis.

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Section: Resultssupporting

confidence: 91%

“…EMs were found to be independent protective factors for patients with VHL (HR=0.553, 95% CI 0.324 to 0.943, p=0.03). Additionally, we found that a positive family history and a low onset age (≤30 years) were independent risk factors for patients with VHL, which were coincident with previous analyses27(table 3).…”

Section: Resultssupporting

confidence: 89%

Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study

Xie

Ma²,

Zhang³

et al. 2020

J Med Genet

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“…In addition, two asymptomatic VHL gene carriers (F2-III1, 5 years of age, p.N78S; F3-IV2, 21 years of age, p.R167Q) were identified via gene testing. Early diagnosis and genetic counseling, regular cancer screening and surveillance are therefore helpful for disease management and for the improvement of prognosis (40).…”

Section: Discussionmentioning

confidence: 99%

Clinical diagnosis, treatment and screening of the VHL gene in three von Hippel‑Lindau disease pedigrees

et al. 2020

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The present study aimed to investigate the clinical characteristics of von Hippel-Lindau (VHL) disease and the clinical significance of VHL gene detection. The clinical materials of patients with VHL disease were collected from 3 different families between May 1985 and October 2017. A systematic pedigree study and VHL gene detection at the germline level were performed together with a literature review. Of the 22 patients from 3 VHL pedigrees, 10 exhibited VHL gene mutations (3 genotypes) at the germline level. The genotypes of pedigree were VHL-p.R161Q (c.482G>A), VHL-p.N78S (c.233A>G), and VHL-p.R167Q (c.500G>A). During the follow-up period, the symptoms were stable in 10 patients, including 2 cases of central nervous system hemangioblastomas (CNS-HB), 3 cases of bilateral multiple renal cell carcinoma (RCC) and 5 cases of adrenal pheochromocytoma without local recurrence or distant metastasis. Patients with p.R161Q and p.N78S were not associated with CNS-HB, which was different from the clinical phenotype of previously reported families. RCC were Fuhrman II grade, which was consistent with the previous study. The results of the present study indicated that the standardization of early diagnosis and the improvement of long-term efficacy may be achieved by combining clinical screening and VHL gene detection.

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“…Clinically, the mean life expectancy of VHL patients was reported to be 49 years old in a large cohort 30 years ago. Although there is no cure for the hereditary cancer syndrome, early diagnosis has made the median survival age improve to over 60 years old based on the establishment of active surveillance plans (W ang et al . 2018).…”

Section: Introductionmentioning

confidence: 99%

Intra-familial phenotypic heterogeneity and telomere abnormality in von Hippel-Lindau disease

Wang

Xiang

et al. 2019

Preprint

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34Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome with poor survival. The 35 current recommendations have proposed uniform surveillance strategies for all patients, neglecting 36 the obvious phenotypic varieties. In this study, we aim to confirm the phenotypic heterogeneity in 37 VHL disease and the underlying mechanism. A total of 151 parent-child pairs were enrolled for 38 genetic anticipation analysis, and 77 sibling pairs for birth order effect analysis. Four statistical 39 methods were used to compare the onset age of patients among different generations and different 40 birth orders. The results showed that the average onset age was 18.9 years earlier in children than 41 in their parents, which was statistically significant in all of the four statistical methods. 42Furthermore, the first-born siblings were affected 8.3 years later than the other ones among the 43 maternal patients. Telomere shortening was confirmed to be associated with genetic anticipation in 44 VHL families, while it failed to explain the birth order effect. Moreover, no significant difference 45 was observed for overall survival between parents and children (p=0.834) and between first-born 46 patients and the other siblings (p=0.390). This study provides definitive evidence and possible 47 mechanisms of intra-familial phenotypic heterogeneity in VHL families, which is helpful to the 48 update of surveillance guidelines. 49 50 4 / 22

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Risk factors for survival in patients with von Hippel-Lindau disease

Cited by 4 publications

References 0 publications

Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study

Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study

Clinical diagnosis, treatment and screening of the VHL gene in three von Hippel‑Lindau disease pedigrees

Intra-familial phenotypic heterogeneity and telomere abnormality in von Hippel-Lindau disease

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