Identification of 3 novel VHL germ-line mutations in Danish VHL patients

BMC Medical Genetics

Research Article

Thomas v O Hansen¹  Lennart Friis-Hansen¹  Finn C Nielsen¹  Mette Dandanell¹  Lone Sunde² 

[1] Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark;Department of Clinical Genetics, Aalborg Hospital, Aalborg, Denmark;

关键词: von Hippel-Lindau disease;    VHL;    Germ-line mutations;    Danish population;   

DOI  :  10.1186/1471-2350-13-54

 received in 2012-01-25, accepted in 2012-06-29,  发布年份 2012

来源: Springer

【 摘 要 】

Backgroundvon Hippel-Lindau (VHL) disease is a hereditary cancer syndrome in which the patients develop retinal and central nervous system hemangioblastomas, pheochromocytomas and clear-cell renal tumors. The autosomal dominant disease is caused by mutations in the VHL gene.MethodsVHL mutational analysis was carried out by sequencing of the coding sequence and by multiplex ligation-dependent probe amplification analysis. The functional consequence of the variants was investigated using in silico prediction tools.ResultsA total of 289 probands suspected of having VHL syndrome have been screened for mutations in the VHL gene. Twenty-six different VHL mutations were identified in 36 families including one in-frame duplication, two frame-shift mutations, four nonsense mutations, twelve missense mutations, three intronic mutations and four large genomic rearrangements. Three of these mutations (c.319 C > T, c.342_343dupGGT and c.520_521dupAA) were novel.ConclusionsIn this study we report the VHL germ-line mutations found in Danish families. We found three novel VHL mutations where two were classified as pathogenic and the latter was classified as a variant of unknown significance. Together, our findings contribute to the interpretation of the potential pathogenicity of VHL germ-line mutations.

【 授权许可】

Unknown   
© Dandanell et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.