Genetic characterization and protein stability analysis of a Chinese family with Von Hippel-Lindau disease

• Published in: Chinese medical journal Vol. 126; no. 19; pp. 3690 - 3693
• Main Authors: Gao, Yong, Huang, Yan-ping, Tu, Xiang-an, Luo, Dao-sheng, Wang, Dao-hu, Qiu, Shao-peng, Xiang, Peng, Li, Wei-qiang, Jan, Rohozinski, Zhang, Yuan-yuan, Sun, Xiang-zhou, Deng, Chun-hua
• Format: Journal Article
• Language: English
• Published: China Reproductive Medicine Center, The Key Laboratory for Reproductive Medicine of Guangdong Province, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China(Gao Y)%Shanghai Institute of Andrology, Renji Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China%Department of Urology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China%Department of Urology, Dongguan People's Hospital, Dongguan, Guangdong 523059, China%Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China 2013
• Subjects: Adult; China; Female; Humans; Male; Middle Aged; Mutation, Missense; PCR产物; Protein Stability; von Hippel-Lindau Disease - genetics; Von Hippel-Lindau Tumor Suppressor Protein - chemistry; Von Hippel-Lindau Tumor Suppressor Protein - genetics; 中国; 基因突变; 家庭成员; 稳定性分析; 蛋白质; 遗传性疾病; 遗传特性; genetic test,protein stability analysis; renal cell carcinoma; Von Hippel-Lindau disease
• ISSN: 0366-6999; 2542-5641; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.20113162

Background Von HippeI-Lindau disease （VHL）,a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems,has rarely been reported in Asia.We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability.Methods Genomic deoxyribonucleic acid （DNA） extracted from peripheral blood was amplified by polymerase chain reaction （PCR） to three exons of the VHL gene in 9 members of the Chinese family with VHL disease.PCR products were directly sequenced.We estimated the effects of VHL gene mutation on the stability of pVHL,which is indicated by the free energy difference between the wild-type and the mutant protein （△△G）.Results The Chinese family was classified as VHL type 1.Three family members,including two patients and a carrier,had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1.This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein.There was low stability of the VHL protein （the △△G was 12.71 kcal/mol） caused by this missense mutation.Conclusions We first reported a family with this VHL gene mutation in Asia.This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma （RCC） phenotype displayed by this family.The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.