Screening for von Hippel-Lindau disease by DNA polymorphism analysis
G. M. Glenn, W. M. Linehan, S. Hosoe, F. Latif, M. Yao, P. Choyke, M. B. Gorin, E. Chew, E. Olfield, C. Manolatos and al. et
Cancer Diagnosis Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md.
OBJECTIVE--Von Hippel-Lindau (VHL) disease is a rare, inherited multisystem
neoplastic disorder. There is no biochemical test available to distinguish
VHL disease gene carriers from their healthy siblings. We evaluated DNA
polymorphism analysis as a method for identifying disease gene carriers.
DESIGN--Prospective comparison of the results of DNA analysis with a
comprehensive clinical screening examination. SETTING--The Clinical Center
of the National Institutes of Health. PATIENTS--Blood was collected from
182 members of 16 families with VHL disease. Forty-eight asymptomatic
individuals, at risk of developing this hereditary illness (with an
affected parent or sibling), were examined for occult disease at the
Clinical Center of the National Institutes of Health and tested by DNA
polymorphism analysis. RESULTS--DNA polymorphism analysis predicted nine
disease gene carriers and 33 individuals with the wild-type (normal) allele
among the 48 individuals at risk of developing VHL disease; the test was
not informative in six individuals. All nine individuals predicted to carry
the VHL gene had evidence of occult disease on clinical examination. There
was no clinical evidence of VHL disease in 32 of 33 individuals predicted
to carry the wild-type allele. CONCLUSIONS--DNA polymorphism analysis can
identify individuals likely to carry the VHL disease gene among
asymptomatic members of disease families. This technique serves to focus
attention on those individuals who require periodic medical examination and
may help to alleviate the morbidity and mortality associated with this
disease.
