Germline mutation of Glu70Lys is highly frequent in Korean patients with von Hippel-Lindau (VHL) disease
| Autor: | Ji I.n. Lee, Chul Lee, Cheol Ryong Ku, Kyu Yeon Hur, Jin Sung Lee, Myung-Shik Lee, Kyo Yeon Koo, Sena Hwang, Yumie Rhee |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty von Hippel-Lindau Disease endocrine system diseases Tumor suppressor gene Genotype DNA Mutational Analysis Biology urologic and male genital diseases Pheochromocytoma Young Adult Germline mutation Asian People Gene Frequency Molecular genetics Hemangioblastoma Republic of Korea Genetics medicine Humans Child neoplasms Allele frequency Genetics (clinical) Germ-Line Mutation Retrospective Studies Middle Aged medicine.disease female genital diseases and pregnancy complications Phenotype Amino Acid Substitution Statistical genetics Von Hippel-Lindau Tumor Suppressor Protein Cancer research Medical genetics Female |
| Zdroj: | Journal of human genetics. 59(9) |
| ISSN: | 1435-232X |
| Popis: | Von Hippel-Lindau (VHL) disease is an inherited tumor syndrome caused by germline mutations in the VHL tumor suppressor gene. It is characterized by hemangioblastoma in the central nervous system and retina, renal cell carcinoma, pancreatic tumor and cysts, and pheochromocytoma. In this study, we detected 26 germline mutations in the VHL gene of Korean patients, of which 1 was a novel mutation, c.417_418insT. We also integrated our data from this study with the published literature to identify 55 VHL germline mutations in Koreans, and identified a unique hotspot at codon 70. Nine unrelated patients (9/55, 16.4%) had the same amino-acid substitution at codon 70 (Glu70Lys) and showed VHL type 1 phenotypes. Although this mutation was shown to have a mild effect on VHL function, four of the nine patients (44.4%) subsequently developed multiple central nervous system hemangioblastomas or retinal hemangioblastoma. However, this hotspot has not been identified in Chinese or Japanese patients. This study provides information on the spectrum of VHL mutations in Korean VHL disease and contributes to a better understanding of VHL disease in terms of improvements in the clinical management of VHL families. |
| Databáze: | OpenAIRE |
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