Genotype-Phenotype Variability in Birt-Hogg-Dubé syndrome

Devaney, Mark (2014). Genotype-Phenotype Variability in Birt-Hogg-Dubé syndrome. University of Birmingham. M.Phil.

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Birt-Hogg-Dubé Syndrome (OMIM: 135150) is the result of heterozygous germline mutations within the Folliculin gene on 17p11.2 and presents with a classic clinical triad of symptoms: Kidney neoplasia, spontaneous pneumothorax and fibrofolliculomas (benign skin growths). BHD displays no correlation between the type of mutation of the Folliculin gene and the phenotype; patients with the same mutations can present with disparate phenotypes. There is a known age-dependant penetrance present in BHD. Patients with BHD syndrome have an increased risk of Renal Cell Carcinoma (RCC) and associations with Colorectal cancers have been found. This study aims to investigate the potential of this genotype-phenotype variability in two ways. Firstly, it uses Sanger sequencing to test patients for germline polymorphisms known to be associated with susceptibility to renal tumours or melanomas to detect a correlation between possible "genetic modifiers" and risk of skin and renal tumours in BHD syndrome. Secondly investigating the genetic changes involved in renal tumourigenesis in BHD syndrome and sporadic kidney cancer. None of the high risk candidate genes were associated with increased risk of tumours in BHD patients. Sequencing of a BHD sporadic kidney tumour implicated ARHGEF5 in both BHD and sporadic renal tumourigenesis.

Type of Work: Thesis (Masters by Research > M.Phil.)
Award Type: Masters by Research > M.Phil.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine
Funders: None/not applicable
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)


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