Related Experiment Video
Updated: Jun 20, 2026
09:37
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
Genotype-phenotype correlations in VHL exon deletions
Alisdair McNeill1, Eleanor Rattenberry, Richard Barber
1Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
American Journal of Medical Genetics. Part A
|September 19, 2009
Summary
Von Hippel-Lindau (VHL) syndrome, a genetic disorder, has subtypes. Large VHL gene deletions including C3orf10 correlate with a lower risk of renal cell carcinoma (RCC), suggesting a new subtype (Type 1B).
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Von Hippel-Lindau (VHL) syndrome is an inherited cancer predisposition caused by VHL gene mutations.
- VHL syndrome exhibits variable clinical presentations, leading to classification into subtypes (Types 1, 2A-C) based on genotype-phenotype correlations.
- Type 1 VHL is linked to deletions/truncating mutations, increasing risks for hemangioblastomas and renal cell carcinoma (RCC), but not pheochromocytoma.
Purpose of the Study:
- To investigate the clinical significance of large VHL gene deletions, specifically those involving C3orf10 (HSPC300).
- To determine if contiguous loss of C3orf10 alongside VHL gene deletions impacts the risk of developing renal cell carcinoma (RCC).
Main Methods:
- Retrospective review of molecular and clinical data from 127 individuals with germline VHL gene deletions.
- Comparison of renal cell carcinoma (RCC) and hemangioblastoma risks between patients with VHL deletions involving C3orf10 and those with deletions not involving C3orf10.
Main Results:
- Large VHL gene deletions encompassing C3orf10 were associated with a significantly reduced lifetime risk of renal cell carcinoma (RCC) compared to deletions without C3orf10.
- The risk of developing hemangioblastomas remained similar between the two groups of VHL deletion patients.
- These findings support the hypothesis that C3orf10 loss influences VHL syndrome phenotype, particularly RCC risk.
Conclusions:
- Germline VHL gene deletions involving a contiguous loss of C3orf10 are associated with a lower risk of renal cell carcinoma (RCC).
- This specific genetic profile may warrant classification as a distinct subtype, potentially Type 1B, of Von Hippel-Lindau (VHL) syndrome.
- Further research into the role of C3orf10 in VHL pathogenesis is indicated to refine understanding and management strategies.
Related Concept Videos
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
01:11Genetic Lingo
Overview
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
02:32Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...