Genotype–phenotype analysis of von Hippel–Lindau syndrome in fifteen Indian families

Vikkath, Narendranath; Valiyaveedan, Sindhu Govindan; Nampoothiri, Sheela; Radhakrishnan, Natasha; Pillai, Gopal S; Nair, Vasantha; Pooleri, Ginil Kumar; Mathew, Christopher G.; Menon, Krishnakumar N.; Ariyannur, Prasanth S.; Pillai, Ashok

doi:10.1007/s10689-015-9806-z

Cited by 15 publications

(16 citation statements)

References 45 publications

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“…Fifteen articles from nine different countries (Chacon‐Camacho et al, ; Chen et al, ; Gergics et al, ; Gomy et al, ; Huang et al, ; Hwang et al, ; Leonardi, Martella, Tosatto, & Murgia, ; Levine, Collins, Horton, & Schimke, ; Prasad et al, ; Rasmussen et al, ; Ruiz‐Llorente et al, ; Vikkath et al, ; Wang et al, ; Wu et al, ; Zhang et al, ) reported a vHL cohort with at least one child/adolescent and a total of more than five patients (Table ). In total, 62 patients were identified with a vHL diagnosis before 18 years, and information about their ages, genotypes, and phenotypes were extracted from the articles when available.…”

Section: Resultsmentioning

confidence: 99%

von Hippel‐Lindau development in children and adolescents

Launbjerg

Bache

Galanakis

et al. 2017

American J of Med Genetics Pt A

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The autosomal dominant von Hippel-Lindau disease (vHL) is associated with a lifelong risk of tumor development, especially retinal and CNS hemangioblastomas, pheochromocytoma, and renal cell carcinoma. Knowledge of paediatric vHL development is limited, and current surveillance guidelines are based on expert opinions. We aimed to describe the course of vHL development in children and adolescents, focusing on age at first manifestation, manifestation frequencies, and types. The prevalence of vHL diagnosis as well as manifestations in childhood were evaluated based on 99 patients, who had started surveillance before 18 years: 37 Danish patients from the national vHL research database and 62 international patients reported in 15 articles. Overall, 70% (69 of 99) developed manifestations before 18 years (median age at first manifestation: 12 years (range: 6-17 years)). Thirty per cent (30 of 99) had developed more than one manifestation type; the most frequent were retinal (34%) and CNS (30%) hemangioblastomas. Among the 37 Danish patients, 85% (97 of 116) of their tumors were asymptomatic. Vision outcome is significantly improved in hemangioblastomas that are treated while still asymptomatic. We agree with current guidelines that retinal surveillance be performed from birth. The patients had their first CNS hemangioblastomas at the median ages of 13-14 years (range: 6-17 years). Further, 11% (4 of 37) of the Danish patients had CNS surgery in their teenage years. Although the cohort is too small to make definite conclusions about specific initiation ages, regular CNS surveillance from vHL patients' teenage years seems clinically relevant.

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Section: Resultsmentioning

confidence: 99%

von Hippel‐Lindau development in children and adolescents

Launbjerg

Bache

Galanakis

et al. 2017

American J of Med Genetics Pt A

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“…A series of studies have reported genotype–phenotype correlations in VHL diseases from different research perspectives or within different ethnic backgrounds (Yoshida et al, 2000; Patocs et al, 2008; Gomy et al, 2010; Nordstrom-O’Brien et al, 2010; Vikkath et al, 2015). For example, a retrospective study that included 63 VHL patients from two large VHL kindreds (family 1: Y112H mutation and family 2: Y98H mutation) with pheochromocytoma/paraganglioma found that pheochromocytoma expressivity differed by genotype (Nielsen et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Frequent Mutations of VHL Gene and the Clinical Phenotypes in the Largest Chinese Cohort With Von Hippel–Lindau Disease

Hong

Zhou

et al. 2019

Front. Genet.

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Von Hippel–Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age at onset for VHL-associated susceptible organs were calculated and compared. The overall survival of VHL patients was described with Kaplan–Meier curves. Among the 19 frequent germline mutations, there were four hotspot mutation sites (194, 481, 499, and 500). Missense mutations were the most common types of mutations (70.0%) followed by nonsense mutations (20.0%) and splicing mutations (10.0%). Due to the diversity of these mutations, the penetrance for each organ and the age at onset are distinct. Even in cases of similar mutations, variance in the penetrance and age at onset was observed. The mean age at death for the patients in this cohort was 42.4 ± 13.5 years, and variability was observed in the Kaplan–Meier curves. We present a precise summary of the phenotypes for the frequent VHL mutations in the largest Chinese VHL cohort, which provides valuable strategies for genetic counseling and clinical surveillance of VHL individuals.

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“…The frequency of VHL mutation event ranges from 46 to 82% of sporadic cases of RCC. Vikkath et al has screened 30 VHL patients and found that RCC is the presenting manifestation in 7 (22.6%) patients [ 4 ]. VHL mutation affects through the hypoxia inducible factor (HIF) and causes changes in various tissue proteins like VEGF, PDGF, TGF, Fibronectin and others.…”

Section: Introductionmentioning

confidence: 99%

Fibronectin protein expression in renal cell carcinoma in correlation with clinical stage of tumour

2018

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BackgroundCarcinogenesis is a multistep process which involves interplay between the tumour cells and the matrix proteins. This occurs by adherence between the tumour cells and proteins in the extracellular matrix. VHL mutation affects through the hypoxia inducible factor (HIF) and causes changes in various tissue proteins like VEGF, PDGF, TGF, Fibronectin and others. As not much literature is available, we aim to quantify the changes of fibronectin protein in renal cell carcinoma (RCC) tissue.MethodsThis Prospective unbalanced case control study was conducted over a period of 18 months from April 2016 to September 2017. The patients undergoing nephrectomy for the diagnosis of RCC were included in the study after obtaining written informed consent. Patients were excluded from study, if normal renal tissue could not be identified in the resected kidney and if the artery clamp time to retrieval of tissue was more than 30 min. Fibronectin protein is estimated in the tumour tissue by gel electrophoresis and western blotting which is compared with that of normal kidney tissue of the same kidney. Results have been expressed as absolute values with standard deviation and relative expression (RE).ResultsOf the 21 patients analysed 15 showed an increase in fibronectin expression in the renal tumour tissue while 6 did not. The mean expression of Fibronectin protein has increased 1.5 times in the tumour tissue when compared with the normal tissue. The increase was 1.54 times in early tumours compared to 1.37 times in advanced tumours of RCC.ConclusionsFibronectin showed a 1.5 times increase in the tumour compared to normal. This increase is more in Stage 1&2 tumours when compared to the Stage 3&4 tumours.Electronic supplementary materialThe online version of this article (10.1186/s40364-018-0137-8) contains supplementary material, which is available to authorized users.

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Genotype–phenotype analysis of von Hippel–Lindau syndrome in fifteen Indian families

Cited by 15 publications

References 45 publications

von Hippel‐Lindau development in children and adolescents

von Hippel‐Lindau development in children and adolescents

Frequent Mutations of VHL Gene and the Clinical Phenotypes in the Largest Chinese Cohort With Von Hippel–Lindau Disease

Fibronectin protein expression in renal cell carcinoma in correlation with clinical stage of tumour

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