Clinical characteristics of ocular angiomatosis in von Hippel-Lindau disease and correlation with germline mutation

被引:118
作者
Webster, AR
Maher, ER
Moore, AT
机构
[1] Addenbrookes Hosp, Dept Ophthalmol, Cambridge CB2 2QQ, England
[2] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
[3] Univ Birmingham, Dept Paediat & Child Hlth, Div Med & Mol Genet, Birmingham, W Midlands, England
关键词
D O I
10.1001/archopht.117.3.371
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Objectives: To examine the epidemiologic and clinical characteristics of the ocular manifestations of von Hippel-Lindau (VHL) disease and to detect phenotype-genotype relationships of disease severity. Design: A cross-sectional clinical and molecular genetic study. Patients and Methods: One hundred eighty-three affected VHL gene carriers from 81 unrelated pedigrees were interviewed and examined; clinical data were also obtained from 12 living and 39 deceased affected relatives. DNA extracted from venous blood was used to identify mutations in the VHL gene. Results: The prevalence of ocular angiomatosis (hemangioblastomas) in von Hippel-Lindau disease was 67.8% (124/183), and the mean number of angiomas in gene carriers was 1.85 (range, 0-15). Neither prevalence nor angioma count increased with age. Severe vision loss in 1 or both eyes was associated with presentation at a young age. The cumulative probability of incurring vision loss by age 50 years was 35% in all gene carriers, 55% in those with angiomatosis, and significantly worse in those coming to us with symptoms. Angiomas were nonrandomly distributed in the fundus, occurring rarely at the posterior pole (1% of retinal tumors) and commonly on the optic disc (8% of eyes) and supratemporal retina. Complications of ocular angiomatosis included disc and retinal neovascularization; secondary angioma formation; retinal detachment, exudation, and membrane; and retinal and vitreous hemorrhage. Germ-line VHL mutations were detected in 161 of 183 patients and 69 (85%) of 81 pedigrees and included deletions (n = 16), missense (mutations causing amino acid substitutions; n = 24), nonsense (premature stop codons; n = 15), frameshift (n = 13), and splice-site (n = 1) mutations. There was no association between the type or position of mutation and the severity of ocular angiomatosis. Conclusions: A systematic clinical description of a large cohort of VHL gene carriers further defines the ocular phenotype. There is no general influence of germline mutation on severity of ocular disease in VHL. Clinical Relevance: The ophthalmic and molecular genetic description of patients with VHL disease.
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页码:371 / 378
页数:8
相关论文
共 28 条
[1]  
Aiello LP, 1997, INVEST OPHTH VIS SCI, V38, P1647
[2]   VON HIPPEL-LINDAU (VHL) DISEASE WITH PHEOCHROMOCYTOMA IN THE BLACK-FOREST REGION OF GERMANY - EVIDENCE FOR A FOUNDER EFFECT [J].
BRAUCH, H ;
KISHIDA, T ;
GLAVAC, D ;
CHEN, F ;
PAUSCH, F ;
HOFLER, H ;
LATIF, F ;
LERMAN, MI ;
ZBAR, B ;
NEUMANN, HPH .
HUMAN GENETICS, 1995, 95 (05) :551-556
[3]   GERMLINE MUTATIONS IN THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE - CORRELATIONS WITH PHENOTYPE [J].
CHEN, F ;
KISHIDA, T ;
YAO, M ;
HUSTAD, T ;
GLAVAC, D ;
DEAN, M ;
GNARRA, JR ;
ORCUTT, ML ;
DUH, FM ;
GLENN, G ;
GREEN, J ;
HSIA, YE ;
LAMIELL, J ;
LI, H ;
WEI, MH ;
SCHMIDT, L ;
TORY, K ;
KUZMIN, I ;
STACKHOUSE, T ;
LATIF, F ;
LINEHAN, WM ;
LERMAN, M ;
ZBAR, B .
HUMAN MUTATION, 1995, 5 (01) :66-75
[4]  
CROSSEY PA, 1994, HUM MOL GENET, V3, P1303
[5]   TWIN VESSELS IN VONHIPPEL-LINDAU DISEASE [J].
DEJONG, PTVM ;
VERKAART, RJF ;
VANDEVOOREN, MJ ;
MAJOORKRAKAUER, DF ;
WIEGEL, AR .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1988, 105 (02) :165-169
[6]  
Hippel E., 1904, Graefes Archiv Clin Exp Ophthalmol, V(59), P83, DOI DOI 10.1007/BF01994821
[7]   CEREBELLAR HEMANGIOBLASTOMA AND VONHIPPEL-LINDAU DISEASE [J].
HUSON, SM ;
HARPER, PS ;
HOURIHAN, MD ;
COLE, G ;
WEEKS, RD ;
COMPSTON, DAS .
BRAIN, 1986, 109 :1297-1310
[8]  
Jones Michael H., 1992, Human Molecular Genetics, V1, P131, DOI 10.1093/hmg/1.2.131
[10]   IDENTIFICATION OF THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE [J].
LATIF, F ;
TORY, K ;
GNARRA, J ;
YAO, M ;
DUH, FM ;
ORCUTT, ML ;
STACKHOUSE, T ;
KUZMIN, I ;
MODI, W ;
GEIL, L ;
SCHMIDT, L ;
ZHOU, FW ;
LI, H ;
WEI, MH ;
CHEN, F ;
GLENN, G ;
CHOYKE, P ;
WALTHER, MM ;
WENG, YK ;
DUAN, DSR ;
DEAN, M ;
GLAVAC, D ;
RICHARDS, FM ;
CROSSEY, PA ;
FERGUSONSMITH, MA ;
LEPASLIER, D ;
CHUMAKOV, I ;
COHEN, D ;
CHINAULT, AC ;
MAHER, ER ;
LINEHAN, WM ;
ZBAR, B ;
LERMAN, MI .
SCIENCE, 1993, 260 (5112) :1317-1320