RT Journal Article
SR Electronic
T1 Detailed genetic mapping of the von Hippel-Lindau disease tumour suppressor gene.
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 104
OP 107
DO 10.1136/jmg.30.2.104
VO 30
IS 2
A1 F M Richards
A1 E R Maher
A1 F Latif
A1 M E Phipps
A1 K Tory
A1 M Lush
A1 P A Crossey
A1 B Oostra
A1 P Enblad
A1 K H Gustavson
YR 1993
UL http://jmg.bmj.com/content/30/2/104.abstract
AB Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited familial cancer syndrome characterised by a predisposition to the development of retinal, cerebellar, and spinal haemangioblastomas, renal cell carcinoma, and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p25-p26 and flanking markers identified. We report the detailed genetic mapping of the VHL disease locus in 38 families. Significant linkage was detected between VHL disease and D3S601 (Zmax = 18.86 at theta = 0.0, CI 0.0-0.025), D3S18 (Zmax = 11.42 at theta = 0.03, CI 0.005-0.08), RAF1 (Zmax = 11.02 at theta = 0.04, CI 0.007-0.01), and D3S1250 (Zmax = 4.73 at theta = 0.05, CI 0.005-0.15). Multipoint linkage analysis mapped the VHL disease locus between D3S1250 and D3S18 close to D3S601. There was no evidence of locus heterogeneity. This study has (1) confirmed the tight linkage between VHL disease and D3S601, (2) identified D3S1250 as the first marker telomeric to RAF1 which maps centromeric to the VHL disease gene, and (3) narrowed the target region for isolation of the VHL disease gene by positional cloning techniques to a 4 cM interval between D3S1250 and D3S18. These findings will improve the clinical management of families with VHL disease by improving the accuracy of presymptomatic diagnosis using linked DNA markers, and will enhance progress towards isolating the VHL disease gene.