WBR0109

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 40 year old man presents to his local physician complaining of fatigue, malaise and constipation. The patient has undergone a 15 lbs weight loss over the past three months. The patient’s blood pressure is 140/100. Laboratory analysis is notable for a creatinine of 1.5 and BUN of 25. Urinalysis reveals free red cells without casts. An MRI of the abdomen shows bilateral solid renal consolidations. Renal biopsy reveals dysplastic clear cells with several mitotic figures per high powered field. In which of the following genes does this patient most likely harbor a germline defect?]]
Answer A	AnswerA::TSC1
Answer A Explanation	AnswerAExp::Incorrect - mutations of TSC1 cause tuberous sclerosis
Answer B	AnswerB::p53
Answer B Explanation	AnswerBExp::Incorrect - mutations of p53 cause Li-Fraumeni syndrome
Answer C	AnswerC::Rb
Answer C Explanation	AnswerCExp::Incorrect - mutations of Rb cause familial retinoblastoma
Answer D	AnswerD::PTEN
Answer D Explanation	AnswerDExp::Incorrect - mutations of PTEN cause Cowden syndrome.
Answer E	AnswerE::VHL
Answer E Explanation	AnswerEExp::Correct - Bilateral renal cell carcinoma is highly specific for Von Hippel Lindau syndrome, caused by mutations in the eponymous VHL gene.
Right Answer	RightAnswer::E
Explanation	[[Explanation::The patient in this vignette is experiencing the symptoms of renal compromise due to bilateral renal cell carcinoma. Bilateral renal cell carcinoma is highly specific for Von Hippel Lindau syndrome. Von Hippel–Lindau (VHL) disease is a rare, autosomal dominant genetic condition that predisposes individuals to benign and malignant tumours. The most common tumours found in VHL are central nervous system and retinal hemangioblastomas, clear cell renal carcinomas, pheochromocytomas, pancreatic neuroendocrine tumours, pancreatic cysts, endolymphatic sac tumors and epididymal papillary cystadenomas. The disease is caused by mutations of the von Hippel–Lindau tumor suppressor (VHL) gene on the short arm of chromosome 3. These mutations cause constitutive signaling of hypoxia inducible factor. Educational Objective: Bilateral renal cell carcinoma is highly specific for Von Hippel Lindau syndrome, caused by mutations in the eponymous VHL gene. References: First Aid 2012 page 90. Educational Objective: References: ]]
Approved	Approved::Yes
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