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Genotype-Phenotype Correlations Among Two Large Western Pennsylvania Von Hippel-Lindau Disease (VHL) Type 2A Kindreds with High Incidence of Pheochromocytoma and Different Missense Mutations in the VHL Gene

Nielsen, Sarah Marie (2010) Genotype-Phenotype Correlations Among Two Large Western Pennsylvania Von Hippel-Lindau Disease (VHL) Type 2A Kindreds with High Incidence of Pheochromocytoma and Different Missense Mutations in the VHL Gene. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Nielsen, Sarah Mariesnielsen412@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCarty, Sally Ecartyse@upmc.eduSECARTY
Committee MemberThull, Darcy Ldthull@mail.magee.edu
Committee MemberFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberFerrell, Robert Erferrell@pitt.eduRFERRELL
Date: 28 June 2010
Date Type: Completion
Defense Date: 16 April 2010
Approval Date: 28 June 2010
Submission Date: 9 April 2010
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: hemangioblastoma; pheochromocytoma; VHL type 2A
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04092010-123638/, etd-04092010-123638
Date Deposited: 10 Nov 2011 19:35
Last Modified: 19 Dec 2016 14:35
URI: http://d-scholarship.pitt.edu/id/eprint/6933

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