Open AccessMolecular Genetic Diagnosis of von Hippel‐Lindau Disease: Analysis of Five Japanese Families
Author(s) -
Kanno Hiroshi,
Shuin Taro,
Kondo Keiichi,
Ito Susumu,
Hosaka Masahiko,
Torigoe Soichiro,
Fujii Satoshi,
Tanaka Yoshihide,
Yamamoto Isao,
Kim Ilu,
Yao Masahiro
Publication year - 1996
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1996.tb00240.x
Subject(s) - missense mutation , exon , von hippel–lindau disease , genetics , frameshift mutation , germline mutation , mutation , biology , germline , splice site mutation , gene , mutation testing , gene mutation , disease , medicine , alternative splicing , pathology
We analyzed deoxyribonucleic acids from blood samples of five Japanese von Hippel‐Lindau (VHL) disease families (three familial cases, two new mutations) for the presence of VHL gene mutations by single‐strand conformational polymorphism analysis and direct sequencing. Four of the five families showed germ line mutations in VHL gene, comprising 2 missense mutations, 1 deletion, and 1 splice‐site mutation. Two families had VHL gene mutations at exon 1; 1 family at exon 3; and 1 family at the splice‐site adjacent to exon 3. Presymptomatic patients were accurately diagnosed by these methods. However, one family did not show a VHL gene mutation in the germ line but showed a somatic mutation at exon 2 in the hemangioblastoma tissue. The consequence of the somatic mutation was a microdeletion leading to a frameshift mutation. Our study is the first report of VHL gene analyses of Japanese VHL disease families, and suggests that not only germ line mutation, but also somatic mutation can lead to development of a tumor associated with the VHL disease.