Three novel VHL germline mutations in Korean patients with von Hippel-Lindau disease and pheochromocytomas.
Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with germline mutations in the VHL gene. VHL disease, as well as several other cancer syndromes, has been associated with an increased risk of pheochromocytomas, which are catecholamine-secreting tumors of the adrenal gland. VHL disease genotype-phenotype correlations have been well established based on the type of mutations in the VHL gene. However, although many groups have reported VHL germline mutations in different countries, no previous report has described VHL gene mutations in VHL disease and/or pheochromocytoma patients in Korea. In this study, we used direct sequencing to investigate VHL germline mutations in Korean patients with VHL disease or pheochromocytomas (11 VHL patients and 3 additional members from 7 families, 2 patients from 1 family with familial pheochromocytoma, and 2 cases of isolated pheochromocytoma). We found a total of 7 VHL germline mutations (6 missense and 1 frameshift), 3 of which were novel (323_324delGC, 355T>C and 361G>A). No VHL germline mutation was found in the 2 patients with isolated pheochromocytomas and paragangliomas. This study provides informative data for VHL germline mutations and VHL-related phenotypes in Korea.
Kang
Hio Chung
HC
Korean Hereditary Tumor Registry, Cancer Research Institute, Seoul National University, Seoul.
Kim
Il-Jin
IJ
Park
Jae-Hyun
JH
Shin
Yong
Y
Jang
Sang-Geun
SG
Ahn
Sun-A
SA
Park
Hye-Won
HW
Lim
Sun-Kyung
SK
Oh
Seung Keun
SK
Kim
Dae Jung
DJ
Lee
Kwan Woo
KW
Choi
Young-Sik
YS
Park
Young Joo
YJ
Lee
Min Ro
MR
Kim
Duck-Woo
DW
Park
Jae-Gahb
JG
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism; D000328:Adult; D002395:Catecholamines / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D020125:Mutation, Missense; D010235:Paraganglioma / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
D002395:Catecholamines; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human