Von Hippel-Lindau disease (VHL) type 2A is a rare inherited tumor predisposition syndrome, which is primarily associated with benign tumors of the blood vessels of the central nervous system and eyes and benign tumors of the adrenal gland, though renal cell carcinoma (RCC) can also be part of this tumor spectrum. Two large regional VHL type 2A kindreds have been assessed over decades at the University of Pittsburgh. Both kindreds have markedly high rates of adrenal and extra-adrenal pheochromocytoma, and almost no cases of RCC. By mutational analysis, each kindred has a separate disease-causing missense mutation of the VHL gene: Y112H (334 T to C) in Family 1, and Y98H (292 T to C) in Family 2. Both gene changes arise from a tyrosine to histidine substitution in exon 1 of the VHL gene on chromosome 3p25. Phenotypic expression in the family with Y112H (Family 1) has been described in the past, however the phenotype related to Y98H (Family 2) has not heretofore been described. Although these mutations are similar and occur within the same region of the gene, I hypothesize that there are differences in disease expression between the families, particularly related to pheochromocytoma. The aim of this study is to evaluate the phenotypic expression of VHL in these genotypically different VHL type 2A kindreds.
Public Health Significance:
Although VHL disease is clinically rare, the treasure trove of information provided by large VHL type 2A kindreds can help to clarify phenotype, penetrance, and survival patterns as well as further define surveillance algorithms.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04092010-123638 |
| Date | 28 June 2010 |
| Creators | Nielsen, Sarah Marie |
| Contributors | Robert E. Ferrell, Darcy L. Thull, MS, GCG, Sally E. Carty, MD, Eleanor Feingold, PhD |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04092010-123638/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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