Document Detail


Genotype-phenotype correlations in VHL exon deletions.
MedLine Citation:
PMID:  19764026     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Von Hippel-Lindau (VHL) syndrome is a dominantly inherited familial cancer syndrome caused by mutations in the VHL gene. VHL syndrome displays marked variation in expression and analysis of genotype-phenotype correlations have led to the concept of four subtypes of VHL syndrome (Types 1, 2A-C). Type 2 subtypes of VHL syndrome are characterized by the presence of pheochromocytoma and the three Type 2 subtypes are associated with differing risks of hemangioblastoma and renal cell carcinoma (RCC). Type 2 VHL syndrome is usually associated with surface missense mutations. Type 1 VHL syndrome is most commonly caused by germline exon deletions and truncating mutations and is characterized by susceptibility to hemangioblastomas and RCC but not pheochromocytoma. Recently, it has been suggested that large VHL gene deletions involving C3orf10 (HSPC300) might be associated with a low risk of RCC. We have reviewed the molecular and clinical characteristics of 127 individuals with germline VHL gene deletions. Large VHL gene deletions associated with a contiguous loss of C3orf10 were associated with a significantly lower lifetime risk of RCC than deletions that did not involve C3orf10. The risks of hemangioblastomas were similar in both groups. These results add to the growing body of evidence suggesting that patients with VHL syndrome caused by large VHL deletions that include C3orf10 may be designated as having a specific subtype (Type 1B) of the disorder.
Authors:
Alisdair McNeill; Eleanor Rattenberry; Richard Barber; Pip Killick; Fiona MacDonald; Eamonn R Maher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of medical genetics. Part A     Volume:  149A     ISSN:  1552-4833     ISO Abbreviation:  Am. J. Med. Genet. A     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-01     Completed Date:  2009-12-17     Revised Date:  2011-11-03    
Medline Journal Info:
Nlm Unique ID:  101235741     Medline TA:  Am J Med Genet A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2147-51     Citation Subset:  IM    
Affiliation:
Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Gland Neoplasms / complications,  genetics
Carcinoma, Renal Cell / complications,  genetics
Cerebellar Neoplasms / complications,  genetics
Cytoskeletal Proteins / genetics
DNA Mutational Analysis
Exons / genetics
Fanconi Anemia Complementation Group D2 Protein / genetics
Gene Deletion*
Genotype
Germ-Line Mutation
Hemangioblastoma / complications,  genetics
Humans
Kidney Neoplasms / complications,  genetics
Phenotype*
Pheochromocytoma / complications,  genetics
Retinal Neoplasms / complications,  genetics
Von Hippel-Lindau Tumor Suppressor Protein / genetics*
von Hippel-Lindau Disease / classification*,  complications,  genetics
Grant Support
ID/Acronym/Agency:
//Cancer Research UK
Chemical
Reg. No./Substance:
0/BRK1 protein, human; 0/Cytoskeletal Proteins; 0/FANCD2 protein, human; 0/Fanconi Anemia Complementation Group D2 Protein; EC 6.3.2.19/VHL protein, human; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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