scholarly journals rs779805 Von Hippel-Lindau Gene Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association, and Familiar Characteristics

2021 ◽  
Vol 27 ◽  
Author(s):  
Gyula Remenyi ◽  
Zsuzsanna Bereczky ◽  
Réka Gindele ◽  
Aniko Ujfalusi ◽  
Arpad Illes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
Gene Mutations ◽  
Tissue Oxygen ◽  
Blood Cell Count ◽  
Von Hippel Lindau ◽  
The Family ◽  
Red Blood Cell Count ◽  
Vhl Disease ◽  
Secondary Causes

Increased red blood cell count may result from primary erythrocytosis (polycythemia vera), but it is often due to secondary causes with increased erythropoietin levels. Secondary erythrocytosis may also be congenital due to different gene mutations of hemoglobin, hemoglobin stabilization proteins, EPO receptors, or oxygen sensing pathways. Von Hippel- Lindau gene mutation causes altered tissue oxygen sensation in VHL disease, usually with normal hemoglobin. Germline VHL mutations associate with classical VHL disease and represent genetic susceptibility for pheochromocytoma. VHL polymorphisms are mostly considered an innocent phenomenon. Still, some data indicate that these polymorphisms are not always harmless and can occur with prostate, renal, and colon cancer or even with isolated erythrocytosis. Seventy-eight patients referred to our department with elevated hemoglobin were screened for VHL mutations. There were no classical somatic VHL mutations. However, we found heterozygous (GA) or homozygous (AA) rs779805 VHL c.-195G>A polymorphism accompanied by erythrocytosis. These patients are Jak-2 negative, with normal or elevated EPO levels, sometimes with family accumulations and often phlebotomy needs, and in some cases with malignancies in the family. No other cause of erythrocytosis was found. We use phlebotomy regularly, and for those with cardiovascular risk factors, we recommend aspirin.

scholarly journals In silico VHL Gene Mutation Analysis and Prognosis of Pancreatic Neuroendocrine Tumors in von Hippel–Lindau Disease

2017 ◽  
Vol 103 (4) ◽  
pp. 1631-1638 ◽  
Author(s):  
Amit Tirosh ◽  
Mustapha el Lakis ◽  
Patience Green ◽  
Pavel Nockel ◽  
Dhaval Patel ◽  
...  
Keyword(s):  
Disease Progression ◽  
In Silico ◽  
Prediction Models ◽  
Gene Mutations ◽  
Pancreatic Cysts ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Vhl Disease ◽  
The Impact ◽  
Predicted Risk

Abstract Context Patients with von Hippel–Lindau (vHL) disease caused by a missense VHL mutation have a more severe phenotype compared with other VHL mutation types. Objective To define pancreatic neuroendocrine tumor (PNET) aggressiveness according to VHL genotype. Design A prospective natural history study. Setting The National Institutes of Health clinical center. Patients Patients with vHL disease, pancreatic manifestations, and germline missense VHL gene mutations. Intervention In-silico prediction of VHL mutation via five computational prediction models. Patients with >80% prediction for disease-causing mutations in all models [high predicted risk (HPR)] were compared with others [low predicted risk (LPR)]. Main Outcome Measure Rates of metastases, surgical intervention, and disease progression. Results Sixty-nine patients were included: 2 developed metastases, 12 needed surgery, and 31 had disease progression during a median follow-up of 60 months (range 13 to 84 months). Thirteen patients were excluded for low prediction reliability. In the remaining 56 patients (45 with PNETs, 11 with pancreatic cysts), the HPR group (n = 13) had a higher rate of disease progression than the LPR group (n = 43) in multivariable analysis (hazard ratio 3.6; 95% confidence interval, 1.1 to 11.9; P = 0.037). The HPR group also had a higher risk of developing metastases (P = 0.015). Among patients with codon 167 hotspot mutations (n = 26), those in the HPR group had a higher risk for disease progression (P = 0.03) than other patients. Conclusions Computational models for predicting the impact of missense VHL gene mutations may be used as a prognostic factor in patients with PNETs in the context of vHL disease.

scholarly journals Germline VHL gene mutations in Hungarian families with von Hippel–Lindau disease and patients with apparently sporadic unilateral pheochromocytomas

2009 ◽  
Vol 161 (3) ◽  
pp. 495-502 ◽  
Author(s):  
Peter Gergics ◽  
Attila Patocs ◽  
Miklos Toth ◽  
Peter Igaz ◽  
Nikolette Szucs ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Gene Mutations ◽  
Suppressor Gene ◽  
Genetic Alterations ◽  
Missense Mutations ◽  
Gene Deletions ◽  
Von Hippel Lindau ◽  
Hereditary Tumor Syndrome ◽  
Large Gene ◽  
Vhl Disease

ObjectiveVon Hippel–Lindau (VHL) disease is a hereditary tumor syndrome caused by mutations or deletions of theVHLtumor-suppressor gene. GermlineVHLgene alterations may be also present in patients with apparently sporadic pheochromocytoma (ASP), although a wide variation in mutation frequencies has been reported in different patient cohorts.DesignHerein, we report the analysis of theVHLgene in Hungarian families with VHL disease and in those with ASP.MethodsSeven families (35 members) with VHL disease and 37 unrelated patients with unilateral ASP were analyzed. Patients were clinically evaluated and theVHLgene was analyzed using direct sequencing, multiplex ligation-dependent probe amplification, and real-time PCR with SYBR Green chemistry.ResultsDisease-causing genetic abnormalities were identified in each of the seven VHL families and in 3 out of the 37 patients with ASP (one nonsense and six missense mutations, two large gene deletions and one novel 2 bp deletion). Large gene deletions and other genetic alterations resulting in truncated VHL protein were found only in families with VHL type 1, whereas missense mutations were associated mainly, although not exclusively, with VHL type 2B and type 2C.ConclusionsThe spectrum ofVHLgene abnormalities in the Hungarian population is similar to that observed in Western, Japanese, or Chinese VHL kindreds. The presence ofVHLgene mutations in 3 out of the 37 patients with ASP suggests that genetic testing is useful not only in patients with VHL disease but also in those with ASP.

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

2018 ◽  
Vol 55 (5) ◽  
pp. 322-328 ◽  
Author(s):  
Jiang-Yi Wang ◽  
Shuang-He Peng ◽  
Teng Li ◽  
Xiang-Hui Ning ◽  
Sheng-Jie Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Median Survival ◽  
Chinese Patients ◽  
Onset Age ◽  
Von Hippel Lindau ◽  
Risk Of Death ◽  
Truncating Mutation ◽  
Vhl Disease ◽  
Mutation Type

BackgroundHistorically, von Hippel-Lindau (VHL) disease is characterised by a poor survival. Although genotype–phenotype correlation has been described in many studies, the risk factors for VHL survival remain unclear. This study aims to evaluate the median survival of Chinese patients with VHL disease and explore whether VHL survival is influenced by genetic and clinical factors.MethodsIn this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan-Meier plot and Cox regression model were used to evaluate the median survival and assess how survival was influenced by birth year, birth order, sex, family history, mutation type, onset age and first presenting symptom.ResultsThe estimated median life expectancy for Chinese patients with VHL disease was 62 years. Patients with early-onset age, positive family history and truncating mutation types had poorer overall and VHL-related survival. Patients with haemangioblastoma as their first presenting symptom were related to a higher risk of death from central nervous system haemangioblastoma than those with abdominal lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004).ConclusionsThis largest VHL survival analysis indicates that onset age, family history, mutation type and first presenting symptom have an effect on the survival of patients with VHL disease, which is helpful to genetic counselling and clinical decision-making.

scholarly journals Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients

2021 ◽  
pp. jmedgenet-2021-108216
Author(s):  
Kenan Zhang ◽  
Jianhui Qiu ◽  
Wuping Yang ◽  
Kaifang Ma ◽  
Lei Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Risk Factor ◽  
Survival Analysis ◽  
Life Expectancy ◽  
Independent Risk Factor ◽  
Onset Age ◽  
Affected Offspring ◽  
Von Hippel Lindau ◽  
Vhl Disease

BackgroundVon Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome with poor prognosis. The clinical manifestation was found to be more serious in affected offspring of patients with VHL disease, but the risk factors and survival for them have never been reported before. We aimed to explore how these patients were influenced by genetic and clinical factors.MethodsIn this retrospective study, we collected 372 affected offspring of VHL patients from 118 unrelated VHL families. Patients were stratified into different groups based on sets of variables. The age-related risk, overall survival and central nervous systemhaemangioblastoma (CHB)-specific survival were analysed between different groups using Kaplan-Meier survival analysis and Cox regression analysis.ResultsThe estimated median life expectancy and median age of onset for affected offspring of VHL patients were 66 years and 28 years, respectively. The later generation and patients with mutations in exon 3 had an earlier onset age. The first presenting symptom was the only independent risk factor influencing overall survival and CHB-specific survival. Patients that the first presenting symptom is central nervous system (CNS) significantly had a lower life expectancy both in overall survival and CHB-specific survival analysis than abdominal lesions group.ConclusionThis study indicated that affected offspring of VHL patients with CNS as the first presenting symptom was an independent risk factor for overall survival and CHB-specific survival. Generation and mutation region only had an effect on the onset age, which is helpful to clinical decision-making and generate a more precise surveillance protocol.

scholarly journals Macular Perfusion Impairment in Von Hippel-Lindau Disease Suggests a Generalized Retinal Vessel Alteration

2020 ◽  
Vol 9 (8) ◽  
pp. 2677 ◽  
Author(s):  
Elisabetta Pilotto ◽  
Elisabetta Beatrice Nacci ◽  
Alfonso Massimiliano Ferrara ◽  
Gilda De Mojà ◽  
Stefania Zovato ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Gene Mutations ◽  
Retinal Vessel ◽  
Vessel Diameter ◽  
Von Hippel Lindau ◽  
Length Fraction ◽  
Retinal Capillary ◽  
Von Hippel Lindau Disease ◽  
Vasculogenesis And Angiogenesis ◽  
Vhl Disease

Background: To evaluate macular perfusion in patients with Von Hippel–Lindau (VHL) disease. Methods: VHL patients with or without peripheral retinal hemangioblastomas (RHs) were consecutively enrolled. A group of healthy subjects served as controls. Macular perfusion was analyzed by means of OCT angiography (OCTA) in the superficial vascular plexus (SVP), and in the intermediate (ICP) and deep retinal capillary (DCP) plexuses. The following OCTA parameters were measured: Vessel Area Density (VAD), Vessel Length Fraction (VLF), Vessel Diameter Index (VDI) and Fractal Dimension (FD). Results: Sixty-three VHL patients (113 eyes) and 28 healthy controls (56 eyes) were enrolled. All OCTA quantitative parameters were reduced in VHL patients vs. controls, reaching statistical significance for VAD of the SVP (0.348 ± 0.07 vs. 0.369 ± 0.06, p = 0.0368) and VDI of all plexuses (p < 0.03 for all). No significant differences were detected between eyes without or with peripheral RHs. Conclusions: Macular perfusion is reduced in VHL patients demonstrating retinal vessel changes that are independent of the presence of peripheral RHs. VHL gene mutations disrupt the hypoxia-induced (HIF)/vascular endothelium growth factors (VEGF) pathway and the Notch signaling, both essential for the normal retinal vasculogenesis and angiogenesis. Therefore, an anomalous generalized retinal vascular development may be hypothesized in VHL disease.

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

scholarly journals Surgical Treatment of Sialolithiasis Leads to Improvement in the Complete Blood Count

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 414
Author(s):  
Gal Avishai ◽  
Idan Rabinovich ◽  
Hanna Gilat ◽  
Gavriel Chaushu ◽  
Liat Chaushu
Keyword(s):  
Surgical Treatment ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Blood Count ◽  
Complete Blood Count ◽  
Blood Cell Count ◽  
Blood Profile ◽  
Post Procedure ◽  
Red Blood Cell Count ◽  
Anemia Of Inflammation

Sialolithiasis is a chronic disease in which a sialolith (salivary stone) causes recurrent inflammation of the affected salivary gland. Anemia of inflammation is a well-described pathology in which a chronic inflammatory disease leads to a reduction in the red blood cell count, hemoglobin and hematocrit values. In this retrospective cohort study, we aim to find whether removal of the sialolith and alleviation of the inflammation affect the complete blood count results. We examined data regarding forty-nine patients who underwent surgery for the removal of a submandibular gland sialolith using the duct-stretching technique. Complete blood counts two years before and after the surgical procedure were collected. The average pre-procedure and post-procedure values were calculated for each patient to establish the average blood profile. The pre- and post-procedure values were compared to evaluate the effect of the surgical treatment on the blood profile. We found that the average blood count values for patients with sialolithiasis were towards the lower end of the normal range. Post-surgery, a significant increase in hematocrit, hemoglobin and red blood cell count was observed, which was more pronounced in the older age group and in patients with co-morbidities. We conclude that sialolith removal surgery is associated with significant improvement in the complete blood count values, especially in the elderly and in patients and with co-morbidities. The speculated pathogenesis is relative anemia of inflammation.

scholarly journals Effect of plateletpheresis on hematocrit, hemoglobin and erythrocyte count: Meta-analysis 1980–2018

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alejandro Gil-Betacur ◽  
Carmen Yulieth Mantilla-Gutiérrez ◽  
Jaiberth Antonio Cardona-Arias
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
Red Blood Cell ◽  
Meta Analysis ◽  
Erythrocyte Count ◽  
Blood Cell Count ◽  
Selection Processes ◽  
Negative Effect ◽  
Red Blood Cell Count ◽  
The Mean

AbstractThe effects of platelet donation by apheresis on different parameters of the erythrogram are still unclear. The objective was to meta-analyze the effect of plateletpheresis on hematocrit, hemoglobin, and erythrocyte count, with a systematic review with random effects meta-analysis of the mean difference. The PRISMA guidelines were considered, as well as 133 search strategies on four different databases. Reproducibility was guaranteed and methodological quality was evaluated. Heterogeneity was evaluated with Galbraith and DerSimonian-Laird’s, publication bias with a funnel plot and a Begg’s test, sensitivity analysis and a cumulative meta-analysis were also conducted. Eighteen (18) articles were included, 17 evaluated the effects on hematocrit in 2,564 donors; 13 on hemoglobin in 1,640 donors; and 4 on red blood cell count in 243 donors. A decrease of 2.26% (CI95% = 2.11–2.41) was observed in hematocrit, of 0.80 g/dL (CI95% = 0.75–0.86) in hemoglobin and −0.21 × 1012/L (CI95% = −0.13; −0.29) in red blood cell count. Plateletpheresis has a negative effect on the erythrogram parameters, explained by blood loss in the kits used for the procedure and cell lysis. Such evidence is relevant to secure the efficiency and safety of the procedure, improve selection processes or determine the number of donations that can be performed without affecting donors’ health.

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