Genetic Analysis of von Hippel-Lindau Disease

被引:240
作者
Nordstrom-O'Brien, Morgan
van der Luijt, Rob B. [2 ]
van Rooijen, Ellen [3 ]
van den Ouweland, Ans M. [4 ]
Majoor-Krakauer, Danielle F. [4 ]
Lolkema, Martijn P.
van Brussel, Aram
Voest, Emile E.
Giles, Rachel H. [1 ]
机构
[1] Univ Med Ctr Utrecht, Ctr Canc, Dept Med Oncol, NL-3584 CX Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands
[3] Hubrecht Inst, Utrecht, Netherlands
[4] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands
关键词
Von Hippel-Lindau; VHL; HIF; kidney cancer; hemangioblastoma; pheochromocytoma; TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; GENOTYPE-PHENOTYPE CORRELATIONS; MULTIPLE ENDOCRINE NEOPLASIA; VHL GERMLINE MUTATIONS; SOMATIC MUTATIONS; FAMILIAL PHEOCHROMOCYTOMA; CAPILLARY HEMANGIOBLASTOMAS;
D O I
10.1002/humu.21219
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information. Hum Mutat 31:521-537, 2010. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:521 / 537
页数:17
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