Genotype-phenotype analysis of von Hippel-Lindau syndrome in Korean families: HIF-α binding site missense mutations elevate age-specific risk for CNS hemangioblastoma. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Lee, Jee-Soo; Lee, Ji-Hyun; Lee, Kyu; Kim, Jung; Hong, Joon; Ra, Eun; Seo, Soo; Lee, Seung; Kim, Man; Park, Sung; Seong, Moon-Woo
• Is Part Of: BMC medical genetics. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Genotype-phenotype correlation -- Hypoxia-inducible factor 1 -- von Hippel-Lindau disease -- von Hippel-Lindau Tumor suppressor protein; Medical genetics -- Periodicals; 616.04205
• DOI: 10.1186/s12881-016-0306-2
• Languages: English
• ISSNs: 1471-2350

Abstract

Abstract Background von Hippel-Lindau (VHL) disease is a rare hereditary tumor syndrome caused byVHL gene mutations that is characterized by heterogeneous phenotypes such as benign/malignant tumors of the central nervous system, retina, kidney, adrenal gland, and pancreas. The genotype-phenotype correlation has not been well characterized in the Korean population so far. Therefore, this study aimed to evaluate theVHL mutation spectrum and genotype-phenotype correlations in Korean VHL patients. Methods Thirteen unrelated subjects withVHL mutations were included. Direct sequencing and multiplex ligation-dependent probe amplification were performed. Consequently, the clinical manifestations and family histories of the subjects were evaluated. Results We identified 10 differentVHL mutations. The c.160_161delAT frameshift mutation was novel. Missense mutations clustered in 2 domains (α domain in exon 1; β domain in exon 3). The most frequently observed mutation was c.208G > A (p.Glu70Lys). Milder phenotypes were observed in subjects withde novo mutations. Age-specific risk for CNS hemangioblastoma was significantly higher in subjects carrying missense mutations within the HIF-α binding site (P < 0.05). Conclusions This study provides insight into the genotype-phenotype correlation in that amino acid substitutions in the HIF-α binding site may predispose patients to age-related risks of CNS hemangioblastoma.