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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2016

Open Access 01-12-2016 | Research article

Genotype-phenotype analysis of von Hippel-Lindau syndrome in Korean families: HIF-α binding site missense mutations elevate age-specific risk for CNS hemangioblastoma

Authors: Jee-Soo Lee, Ji-Hyun Lee, Kyu Eun Lee, Jung Hee Kim, Joon Mo Hong, Eun Kyung Ra, Soo Hyun Seo, Seung Jun Lee, Man Jin Kim, Sung Sup Park, Moon-Woo Seong

Published in: BMC Medical Genetics | Issue 1/2016

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Abstract

Background

von Hippel-Lindau (VHL) disease is a rare hereditary tumor syndrome caused by VHL 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 the VHL mutation spectrum and genotype-phenotype correlations in Korean VHL patients.

Methods

Thirteen unrelated subjects with VHL 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 different VHL 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 with de 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.
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Metadata
Title
Genotype-phenotype analysis of von Hippel-Lindau syndrome in Korean families: HIF-α binding site missense mutations elevate age-specific risk for CNS hemangioblastoma
Authors
Jee-Soo Lee
Ji-Hyun Lee
Kyu Eun Lee
Jung Hee Kim
Joon Mo Hong
Eun Kyung Ra
Soo Hyun Seo
Seung Jun Lee
Man Jin Kim
Sung Sup Park
Moon-Woo Seong
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2016
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-016-0306-2

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