MP71-15 VHL GENE MUTATION SPECTRUM AND GENOTYPE-PHENOTYPE CORRELATIONSHIP OF CHINESE VHL PATIENTS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2016MP71-15 VHL GENE MUTATION SPECTRUM AND GENOTYPE-PHENOTYPE CORRELATIONSHIP OF CHINESE VHL PATIENTS Peng Shuanghe, Li Teng, Wang Jiangyi, and Gong Kan Peng ShuanghePeng Shuanghe More articles by this author , Li TengLi Teng More articles by this author , Wang JiangyiWang Jiangyi More articles by this author , and Gong KanGong Kan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1461AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES VHL disease is an autosomal-dominant inherited familial cancer syndrome caused by germline mutations of VHL gene. The VHL gene mutation spectrum and the genotype-phenotype correlationship of VHL patients from the United States, Europe and Japan had been studied and reported, but these character of Chinese people have been unclear because there are few research of large number of VHL families had been done until now. The purpose of our study is to summary the VHL gene mutation spectrum and genotype-phenotype correlationship of Chinese VHL patients by large sample analysis. METHODS We studied 163 unrelated Chinese VHL families from 17 hospitals distributed throughout China, including 89 families diagnosed in our hospital and 83 families from other domestic hospitals gathered by literature summary. Then we made statistical analysis. RESULTS In the 163 unrelated Chinese VHL families, germline mutations were detected in 157 (96.3%) families. Large deletions of the VHL gene were identified in 27/163 (16.6%) of the families. There were 79 unique, intragenic mutations. All intragenic mutations were located between codons 39 and 180. Three regions of the VHL gene had a high mutation density: codons 65-98, codons 161-168 and splice site at the border of exon 1 and 2. The most common intragenic VHL mutations were: Ser65Trp (n=5), delPhe76 (n=4), Ser80Ile (n=4), Arg161stop (n=7), Arg161Gln (n=6), Arg167Trp (n=8), and Arg167Gln (n=6) There were nine hot mutation codons that affected more than 4 families each. Mutations at codon80 and codon167 are highly correlated with pheochromocytoma, while mutations at codon65, codon76, codon86 and codon162 are negatively related to phechromocytoma. Whether mutations at codon161 are in positive correlation or negative correlation with pheochromocytoma depends on the mutation site: the c.481C>T p.Arg161stop mutation is in positive correlation, and the c.482G>A p.Arg161Gln mutation is in negative correlation. The study of genotype-phenotype correlationship is still ongoing now. CONCLUSIONS Our study summarized the VHL gene mutation spectrum and genotype-phenotype correlationship of 163 unrelated Chinese VHL families. The results have similar parts with other people, but also have Chinese characteristic parts. These will add the diversity of VHL germ-line mutations and are beneficial for the pathogenesis research of the disease. The genotype-phenotype correlation findings can help to predict specific organ lesions and the prognosis of VHL patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e921 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Peng Shuanghe More articles by this author Li Teng More articles by this author Wang Jiangyi More articles by this author Gong Kan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...