Germline mutations of the VHL gene in seven Chinese families with von Hippel-Lindau disease

Huang, Yulun; Zhou, Dai; Liu, Jiangang; Zhou, Peng; Li, Xiangdong; Wang, Zhong

doi:10.3892/ijmm.2011.808

Cited by 5 publications

(6 citation statements)

References 15 publications

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“…Currently, nine studies including the present study have been conducted on 77 Chinese families and have described 49 mutations of VHL . [ 19 20 21 22 23 24 25 26 27 ] The mutations were summarized according to the position, nucleotide change, effect on coding sequence, and associated VHL phenotype (s) [ Table 5 ]. Independent of phenotype, the most frequent mutations were p.S65W, p.N78S, p.R161Q and p.R167W.…”

Section: R Esultsmentioning

confidence: 99%

Clinical and Genetic Investigation of a Multi-generational Chinese Family Afflicted with Von Hippel-Lindau Disease

Zhang

et al. 2015

Chinese Medical Journal

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Background:Von Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.Methods:An epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.Results:A five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.Conclusions:The results supported the notion that the genomic sequence that corresponds to the 167th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.

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Section: R Esultsmentioning

confidence: 99%

Clinical and Genetic Investigation of a Multi-generational Chinese Family Afflicted with Von Hippel-Lindau Disease

Zhang

et al. 2015

Chinese Medical Journal

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“…A total of 52 studies, assessing 840 participants with vHL type 2, provided information on the frequency of PPGL. Most of these studies were conducted in Europe ( n =18) ( 16 , 17 , 21 , 25 , 26 , 28 , 29 , 62 , 66 , 68 , 70 , 71 , 72 , 73 , 76 , 83 , 91 , 92 ), followed by Eastern Asia ( n =17) ( 35 , 36 , 40 , 44 , 45 , 47 , 48 , 74 , 75 , 77 , 78 , 79 , 80 , 81 , 82 , 86 , 87 ) and North America ( n =9) ( 53 , 59 , 60 , 61 , 63 , 64 , 65 , 69 , 84 ). All studies assessed patients of all age groups, with the mean onset age of PPGL being 28.8 years (as reported in 21 studies ( 21 , 26 , 35 , 40 , 44 , 47 , 55 , 59 , 60 , 61 , 65 , 67 , 71 , 72 , 74 , 77 , 79 , 85 , 86 , …”

Section: Resultsmentioning

confidence: 99%

“…All studies assessed patients of all age groups, with the mean onset age of PPGL being 28.8 years (as reported in 21 studies ( 21 , 26 , 35 , 40 , 44 , 47 , 55 , 59 , 60 , 61 , 65 , 67 , 71 , 72 , 74 , 77 , 79 , 85 , 86 , 87 , 88 )). Six studies reported a consecutive sample ( 16 , 17 , 29 , 66 , 77 , 78 ), whereas in 39 studies a convenience sample was assessed ( 21 , 25 , 35 , 45 , 47 , 53 , 56 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ).…”

Section: Resultsmentioning

confidence: 99%

“…The frequency of PPGL among participants with vHL type 2 was 60.0% (95% CI = 53.4–66.3%), with moderate heterogeneity being observed ( I 2 = 54.6%) ( 16 , 17 , 21 , 25 , 26 , 28 , 29 , 35 , 36 , 40 , 44 , 45 , 47 , 48 , 53 , 55 , 56 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ) ( Table 1 ). We observed lower heterogeneity in subgroup analyses restricted to convenience sampling ( I 2 = 25.6%) and to patients whose diagnosis was performed only clinically ( I 2 = 23.1%) (Supplementary Table 7).…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-eight studies, with a total of 411 participants with vHL type 2A, reported the frequency of PPGL among these patients ( 16 , 25 , 26 , 28 , 29 , 35 , 36 , 47 , 55 , 60 , 61 , 62 , 63 , 65 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 78 , 79 , 80 , 81 , 82 , 85 , 92 ). The pooled frequency of PPGL among participants with vHL type 2A was 58.2% (95% CI = 49.7–66.3%, I 2 = 36.2%) ( Table 1 ) ( 16 , 25 , 26 , 28 , 29 , 35 , 36 , 47 , 55 , 60 , 61 , 62 , 63 , 65 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 78 , 79 , 80 , 81 , 82 , 85 , 92 ). In most subgroup analysis, moderate heterogeneity was observed ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

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Pheochromocytomas and paragangliomas in von Hippel–Lindau disease: not a needle in a haystack

Castro-Teles

Sousa‐Pinto

Rebelo

et al. 2021

Endocrine Connections

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Objective: Pheochromocytomas are a hallmark feature of von Hippel-Lindau disease (vHL). To our knowledge, this is the first systematic review with meta-analysis evaluating the frequency of pheochromocytomas and/or paragangliomas (PPGL) in patients with vHL, as well as among patients with different vHL subtypes. Design: Systematic review with meta-analysis. Methods: We searched on MEDLINE, Scopus and Web of Science. We included primary studies assessing participants with vHL and reporting on the frequency of PPGL. We performed random-effects meta-analysis to quantitatively assess the frequency of PPGL, followed by meta-regression and subgroup analysis. Risk of bias analysis was performed to assess primary studies’ methodological quality. Results: We included 80 primary studies. In 4263 patients with vHL, the pooled frequency of PPGL was 19.4% (95% confidence interval (CI)=15.9-23.6%, I²=86.1%). The frequency increased to 60.0% in patients with vHL type 2 (95%CI=53.4-66.3%, I²=54.6%) and was determined to be of 58.2% in patients with vHL type 2A (95%CI=49.7-66.3%, I²=36.2%), compared to 49.8% in vHL type 2B (95%CI=39.9-59.7%, I²=42.7%), and 84.1% in vHL type 2C (95%CI=75.1-93.1%, I²=0%). In meta-regression analysis, more recent studies were associated with a higher frequency of PPGL. All studies had at least one internal validity item classified as 'high risk of bias', with 13% studies having low risk of bias in all external validity items. Conclusions: PPGL are a common manifestation of vHL. Despite methodological limitations and differences across primary studies, our results point to the importance of PPGL screening in patients with vHL.

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Supplementary Methods from l-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer

Shim¹,

Livi²,

Rakheja³

et al. 2023

Preprint

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Germline mutations of the VHL gene in seven Chinese families with von Hippel-Lindau disease

Cited by 5 publications

References 15 publications

Clinical and Genetic Investigation of a Multi-generational Chinese Family Afflicted with Von Hippel-Lindau Disease

Clinical and Genetic Investigation of a Multi-generational Chinese Family Afflicted with Von Hippel-Lindau Disease

Pheochromocytomas and paragangliomas in von Hippel–Lindau disease: not a needle in a haystack

Supplementary Methods from l-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer

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