title: Improved detection of germline mutations in Korean VHL patients by multiple ligation-dependent probe amplification analysis.
abstract: von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome characterized by the development of tumors in the eye, brain, spinal cord, inner ear, adrenal gland, pancreas, kidney, and epididymis, associated with germline mutations in the VHL gene. We used sequentially sequencing method and multiple ligation-dependent probe amplification (MLPA) analysis and detected germline mutations in the VHL in 15/15 (100%) of VHL patients fulfilling the clinical criteria. Of the 15 distinct mutations detected, large deletions were detected in 5/15 (33.3%) patients, including 4/15 (26.7%) partial deletions and 1/15 (6.6%) deletion of the entire VHL gene by MLPA and the remainder were point mutations detected by sequencing method, of which five mutations were novel. Using MLPA analysis, we detected large deletions including both partial deletions and complete gene deletion, which has not been reported in Korean VHL patients. In conclusion, sequential application of sequencing method and MLPA analysis might make possible to identify germline mutations in most patients with VHL.
authors.affiliation: Department of Laboratory Medicine, Konyang Univeristy Hospital, College of Medical Science, Konyang University, Daejon, Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017421:Sequence Analysis; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000175:diagnosis / Q000235:genetics*