Screening for von Hippel-Lindau disease by DNA polymorphism analysis.
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.


METHODS
Prospective comparison of the results of DNA analysis with a comprehensive clinical screening examination.


METHODS
The Clinical Center of the National Institutes of Health.


METHODS
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.
Cancer Diagnosis Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md.
G M
GM
Glenn
W M
WM
Linehan
S
S
Hosoe
F
F
Latif
M
M
Yao
P
P
Choyke
M B
MB
Gorin
E
E
Chew
E
E
Olfield
C
C
Manolatos
D004247:DNA / Q000032:analysis*; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D012306:Risk; D006623:von Hippel-Lindau Disease / Q000175:diagnosis* / Q000235:genetics
D004247:DNA