scholarly journals Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions

2004 ◽  
Vol 24 (5) ◽  
pp. 435-436 ◽  
Author(s):  
Catherine Gallou ◽  
Dominique Chauveau ◽  
Stéphane Richard ◽  
Dominique Joly ◽  
Sophie Giraud ◽  
...  
Keyword(s):  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Renal Lesions ◽  
Genotype Phenotype Correlation

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions

2004 ◽  
Vol 24 (3) ◽  
pp. 215-224 ◽  
Author(s):  
Catherine Gallou ◽  
Dominique Chauveau ◽  
Stéphane Richard ◽  
Dominique Joly ◽  
Sophie Giraud ◽  
...  
Keyword(s):  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Renal Lesions ◽  
Genotype Phenotype Correlation

scholarly journals GEN-03 GENOTYPE-PHENOTYPE CORRELATION IN 111 FAMILIES OF VON HIPPEL-LINDAU DISEASE IN JAPAN

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii8-ii8
Author(s):  
Hiroshi Kanno ◽  
Tetsuya Yoshizumi ◽  
Masamichi Shinonaga ◽  
Masahiro Yao
Keyword(s):  
Amino Acids ◽  
Missense Mutation ◽  
Splice Site ◽  
Phenotype Correlation ◽  
Exon 2 ◽  
Endolymphatic Sac Tumor ◽  
Von Hippel Lindau ◽  
Genotype Phenotype Correlation ◽  
Exon 1 ◽  
Vhl Disease

Abstract BACKGROUND AND AIM von Hippel-Lindau (VHL) disease is a hereditary disease which manifest central nervous system (CNS) hemangioblastoma, retinal angioma, renal cell carcinoma (RCC), pheochromocytoma, endolymphatic sac tumor, and pancreas cyst. The VHL gene is located at 3p25.3 and is corresponding to 213 amino acids. Genotype-phenotype correlation analyses of VHL disease have been recently reported from several foreign countries, but the genotype-phenotype correlation has not been characterized since above 10 years ago. Therefore, this study aimed to evaluate the VHL mutation spectrum and genotype-phenotype correlations in Japanese VHL patients. METHODS Blood samples of 111 unrelated families of VHL disease were collected and DNAs were extracted. Direct sequencing and real-time PCR analysis were performed. Consequently, the clinical manifestations and family histories of the subjects were evaluated. RESULTS We identified VHL mutations as follows: missense 47; deletion 17; insertion 5; nonsense 8; splice-site 9; larger deletion 25. At hot-spot codon 167, 4 minsense mutations were identified, with Arg167Trp, 4 cases; Arg167Gln2, 2 cases. At codon 155, splice-site mutations were identified at 6 cases. Mutation sites were distributed in exon 1, 45; exon 2, 21; exon 3, 36. Large deletions were distributed in exon 1 & 2, 1; exon 2& 3, 1; all exons, 11. Genotype-phenotype correlation analysis revealed that age-specific risk and number of CNS hemangioblastoma were significantly higher in subjects carrying missense mutation within HIF-α binding site or non-missense mutation (P < 0.05). In addition, penetrance of RCC was significantly higher in subjects carrying non-missense mutation (P < 0.05). CONCLUSIONS The results of this study were similar to the previous foreign studies. This study provides insight into the genotype-phenotype correlation in that amino acids substitutions in the HIF- α binding and non-sense mutations may predispose VHL patients to age-related risk and number of CNS hemangioblastoma.

Clinical and molecular characterization of Brazilian families with von Hippel-Lindau disease: a need for delineating genotype-phenotype correlation

2010 ◽  
Vol 9 (4) ◽  
pp. 635-642 ◽  
Author(s):  
Israel Gomy ◽  
Greice Andreotti Molfetta ◽  
Ester de Andrade Barreto ◽  
Cristiane Ayres Ferreira ◽  
Dalila Luciola Zanette ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Genotype Phenotype Correlation ◽  
Von Hippel Lindau Disease

scholarly journals Genotype-Phenotype Correlation in Patients With Germline Mutations of VHL, RET, SDHB, and SDHD Genes: Thai Experience

2017 ◽  
Vol 10 ◽  
pp. 117955141770512 ◽  
Author(s):  
Chutintorn Sriphrapradang ◽  
Kitjapong Choopun ◽  
Atchara Tunteeratum ◽  
Thanyachai Sura
Keyword(s):  
Neurofibromatosis Type ◽  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Screening Programs ◽  
Medical Chart Review ◽  
Genotype Phenotype Correlation ◽  
Disease Risks ◽  
Exon 11 ◽  
Bilateral Lesions ◽  
Vhl Disease

Mutations in the VHL, RET, SDHB, and SDHD genes are responsible for von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type 2 (MEN2), and familial paraganglioma, respectively. However, genotype-phenotype correlation data are lacking in Southeast Asia. A retrospective medical chart review was performed on patients referred to the genetics service. We found 35 patients diagnosed with clinical syndromes (16 VHL, 9 MEN2, 9 paragangliomas, and 1 neurofibromatosis type 1). In patients with VHL, 5 known VHL mutations were identified: p.Trp88X, p.Ile151Thr, p.Arg161X, p.Arg167Gln, and p.Leu178Arg. The most frequent RET mutations in patients with MEN2A occurred at codon 634 on exon 11: p.Cys634Tyr, p.Cys634Trp, and p.Cys634Arg. A patient with MEN2B had p.Met918Thr RET mutation. Approximately, 90% of patients with MEN2 had medullary thyroid carcinoma. Pheochromocytoma was found in 55.6% of patients with MEN2, and 60% of them had bilateral lesions. One patient with malignant thoracic paraganglioma had p.Arg46X mutation of SDHB. This study provides mutation phenotypes that offer a useful tool for clinicians and patients to stratify disease risks and tailor screening programs.

Genotype phenotype correlation in Asian Indian von Hippel–Lindau (VHL) syndrome patients with pheochromocytoma/paraganglioma

2017 ◽  
Vol 17 (3) ◽  
pp. 441-449 ◽  
Author(s):  
Nilesh Lomte ◽  
Sanjeet Kumar ◽  
Vijaya Sarathi ◽  
Reshma Pandit ◽  
Manjunath Goroshi ◽  
...  
Keyword(s):  
Asian Indian ◽  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Genotype Phenotype Correlation

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

2020 ◽  
Vol 57 (11) ◽  
pp. 744-751
Author(s):  
Haibiao Xie ◽  
Kaifang Ma ◽  
Jiufeng Zhang ◽  
Baoan Hong ◽  
Jingcheng Zhou ◽  
...  
Keyword(s):  
Binding Site ◽  
Missense Mutation ◽  
Gene Mutation ◽  
Protective Factor ◽  
Phenotype Correlation ◽  
Von Hippel Lindau ◽  
Genotype Phenotype Correlation ◽  
Age Related ◽  
Related Risk ◽  
Vhl Disease

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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