High-resolution chromosome banding and fragile site studies in von Hippel-Lindau syndrome

von Hippel-Lindau syndrome is an autosomal dominant disorder that predisposes to the development of benign and malignant tumors. The gene for von Hippel-Lindau syndrome has not yet been localized and the cytogenetics of this cancer-prone genetic disease have not been fully explored. Therefore, we did high-resolution chromosome banding of lymphocytes from patients from 14 kindreds with von Hippel-Lindau syndrome. There were 18 patients (eight male, and ten female). None of the male patients showed a detectable chromosome abnormality. However, three of the ten female patients had 45,X/46,XX/47,XXX chromosome mosaicism with predominance of the normal cell line. Fragile sites at 10q25 and 16q22 were found but both segregated independently of von Hippel-Lindau syndrome. The location of this disease gene, thus, is still unknown. The tendency to chromosome mosaicism manifest in this study suggests that there is a possible error in controlling somatic chromosome division and that error in mitosis may be causally related to the predisposition to tumor formation in von Hippel-Lindau syndrome.