scholarly journals p.Arg82Leu von Hippel-Lindau (VHL) Gene Mutation among Three Members of a Family with Familial Bilateral Pheochromocytoma in India: Molecular Analysis and In Silico Characterization

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61908 ◽  
Author(s):  
Anulekha Mary John ◽  
George Priya Doss C ◽  
Andrew Ebenazer ◽  
Mandalam Subramaniam Seshadri ◽  
Aravindan Nair ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Molecular Analysis ◽  
In Silico ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Bilateral Pheochromocytoma ◽  
In Silico Characterization

A Unique Case of Renal Carcinoma with Xp11.2 Translocations/TFE3 Gene Fusions in a 3-Year-old Child, with Coexistent von Hippel-Lindau Gene Mutation

2004 ◽  
Vol 7 (4) ◽  
pp. 403-406 ◽  
Author(s):  
Mana M. Parast ◽  
Grant Eudy ◽  
Kenneth W. Gow ◽  
Mahul Amin ◽  
Bahig Shehata
Keyword(s):  
Gene Mutation ◽  
Renal Carcinoma ◽  
Pediatric Population ◽  
Single Point ◽  
Single Point Mutation ◽  
Transcription Factor Gene ◽  
Unique Case ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease

Renal cell carcinomas (RCCs) are rare in the pediatric population; when they occur, a significant percentage are associated with specific cytogenetic abnormalities and germline mutations. These include mutations in the von Hippel-Lindau (VHL) gene and translocations involving the TFE3 transcription factor gene on Xp11.2. Here we report a case of a 3-year-old child with a large renal mass. Histologic examination of the tumor showed a predominantly nested growth pattern with some papillary foci. Cytogenetic analysis revealed a karyotype of t(X;1)(p11.2; p34.3), consistent with a TFE3-associated RCC. Interestingly, sequencing of the patient's VHL gene revealed a single point mutation, previously seen in a subgroup of patients with von Hippel-Lindau disease. This is the first reported case, to our knowledge, of t(X;1)-associated RCC in a patient with concurrent VHL gene mutation.

scholarly journals Identification of a VHL gene mutation in a Chinese family with Von Hippel‑Lindau syndrome

2018 ◽  
Author(s):  
Zhengwen He ◽  
Lu Xia ◽  
Zhiyong Deng ◽  
Aojie Lian ◽  
Zhengmao Hu ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Chinese Family ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Syndrome

scholarly journals Identification of a VHL gene mutation in atypical Von Hippel-Lindau syndrome: genotype–phenotype correlation and gene therapy perspective

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dali Tong ◽  
Yao Zhang ◽  
Jun Jiang ◽  
Gang Bi
Keyword(s):  
Gene Therapy ◽  
Gene Mutation ◽  
Suppressor Gene ◽  
Pancreatic Cysts ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Genetic Examination ◽  
Examination Methods ◽  
Vhl Disease ◽  
Von Hippel Lindau Syndrome

Abstract Background Classical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both. Methods In this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome. Results We reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy. Conclusions Combined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.

Von Hippel-Lindau gene mutation status is associated with a dichotomous response in primary and metastatic tumors in patients receiving bevacizumab and erlotinib for metastatic renal cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15522-15522
Author(s):  
D. Tsavachidou ◽  
N. M. Tannir ◽  
C. G. Wood ◽  
P. Corn ◽  
K. Do ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Renal Cell ◽  
Response To Therapy ◽  
Gene Inactivation ◽  
Vhl Gene ◽  
Von Hippel Lindau

15522 Background: A single arm phase II study is underway evaluating the safety and clinical benefit of presurgical bevacizumab and erlotinib in the management of patients with untreated conventional renal cell carcinoma (RCC). It is not known how the presence or absence of von Hippel Lindau (VHL) mutations affect the response to therapy in the primary or metastatic site, and whether VHL mutational status is predictive for either. Methods: Patients enrolled had conventional RCC, measurable metastatic disease, a primary tumor in place, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. A total of 35 patients were enrolled as of January 8, 2007. Patients were treated with bevacizumab for 4 cycles and erlotinib for 8 weeks, and underwent cytoreductive nephrectomy at week 10 (4 weeks after the last dose of bevacizumab). A VHL gene mutation and methylation analysis was completed on nephrectomy specimens from the first 18 evaluable patients. Patients were grouped according to the presence or absence of functional VHL gene inactivation (mutation and/or methylation). Two-sample T-test and Fisher’s exact test were performed. Results: Ten patients (55%) demonstrated either VHL mutation or methylation ( table 1 ). Patients with no VHL gene inactivation demonstrated more robust primary tumor shrinkage, but did not demonstrate partial responses (PRs). Table 1 . Conclusions: These findings, although preliminary, suggest a dichotomous response in the primary and metastatic disease sites according to VHL functional status. Ongoing evaluation of new treatment strategies using antivascular/targeted agents in RCC may benefit from molecular stratification. [Table: see text] No significant financial relationships to disclose.

Mutation screening of VHL gene in a family with malignant bilateral pheochromocytoma: from isolated familial pheochromocytoma to von Hippel-Lindau disease

2009 ◽  
Vol 8 (4) ◽  
pp. 465-471 ◽  
Author(s):  
Shirin Hasani-Ranjbar ◽  
Mahsa M. Amoli ◽  
Azadeh Ebrahim-Habibi ◽  
Vahid Haghpanah ◽  
Maryam Hejazi ◽  
...  
Keyword(s):  
Mutation Screening ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Bilateral Pheochromocytoma ◽  
Familial Pheochromocytoma ◽  
Von Hippel Lindau Disease

Identification and In Silico Analysis of Novel von Hippel-Lindau (VHL) Gene Variants from a Large Population

2011 ◽  
Vol 75 (4) ◽  
pp. 483-496 ◽  
Author(s):  
Emanuela Leonardi ◽  
Maddalena Martella ◽  
Silvio C.E. Tosatto ◽  
Alessandra Murgia
Keyword(s):  
In Silico ◽  
Large Population ◽  
In Silico Analysis ◽  
Gene Variants ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Silico Analysis

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 Novel gene mutation in von Hippel-Lindau disease – a report of two cases

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jitian Wang ◽  
Wenjie Cao ◽  
Zhaoxia Wang ◽  
Hong Zhu
Keyword(s):  
Gene Mutation ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Gene Mutations ◽  
Neoplastic Disease ◽  
Malignant Tumours ◽  
Mutation Site ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Clinical Phenotypes

Abstract Background Von Hippel-Lindau (VHL) syndrome is a familial autosomal dominant hereditary neoplastic disease caused by mutations in the VHL gene. Approximately 503 kinds of VHL gene mutations have been reported. Different types of mutations manifest various clinical phenotypes, from benign to malignant tumours or coexisting cysts. Thus, a gene mutation test is essential in the diagnosis of VHL syndrome. Case presentation We reported two cases in which a novel mutation site in the c530-536delGACTGGA region in exon 3 of the VHL gene resulted in the development of VHL syndrome. According to the ACMG guidelines, this variation is pathogenic and consistent with autosomal dominant inheritance. This variation has not been reported anywhere in the databases or literature. Conclusion This report will add a new mutation site to VHL gene databases. The newly added gene mutation and its associated clinical phenotypes will help improve the accuracy of VHL diagnosis and benefit the community of VHL gene mutation carriers.

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