WBR0116

Author	[[PageAuthor::Mahmoud Sakr (Reviewed by Will J Gibson and Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Gastrointestinal
Prompt	[[Prompt::A 33-year-old Caucasian female presents with diarrhea and foul-smelling bulky stools for the past 3 weeks. She has tried several over the counter medications with no relief. Yesterday, she noticed an eruption of intensely pruritic papules and vesicles on her elbows, dorsal forearms and back. She recalls that her older brother has suffered from a similar illness for approximately 5 years. Her vital signs and initial labs are unremarkable. Serologic testing revealed elevated levels of IgA tissue transglutaminase antibodies. Which of the following gene mutations most likely predisposed this patient's condition?]]
Answer A	AnswerA::HLA DQ2 gene
Answer A Explanation	[[AnswerAExp::This patient suffers from celiac disease or gluten-sensitive enteropathy, which is genetically predisposed by HLA DQ2 or HLA DQ8 gene subtypes.]]
Answer B	AnswerB::IBD1 gene
Answer B Explanation	AnswerBExp::IBD1 encodes an intracellular pattern recognition receptor (NOD2). IBD1 mutations are associated with inflammatory bowel diseases.
Answer C	AnswerC::HLA-DR2
Answer C Explanation	[[AnswerCExp::The HLA-DR2 variant is associated with inflammatory bowel disease.]]
Answer D	AnswerD::APC gene
Answer D Explanation	[[AnswerDExp::APC gene mutations predispose to familial adenomatous polyposis.]]
Answer E	AnswerE::MSH2 gene
Answer E Explanation	[[AnswerEExp::MSH2 gene mutation is associated with Hereditary nonpolyposis colorectal cancer. MSH2 encodes a DNA mismatch repair enzyme.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::This patient suffers from celiac disease or gluten-sensitive enteropathy. Celiac disease is an autoimmune disease of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward. Symptoms include pain and discomfort in the digestive tract, chronic diarrhea, failure to thrive (in children), anemia and fatigue, but these may be absent, and symptoms in other organ systems have been described. The greatest risk factor for celiac disease is another family member with celiac disease. The second most influential risk factor is the presence of the HLA-DQ2 subtype. Celiac disease is genetically predisposed by HLA-DQ2 or HLA-DQ8 HLA subtypes. HLA associations are commonly tested on the USMLE. One useful mnemonic for the HLA associations is DR = MD..AAH HLA Subtype Associated disease HLA-DR2 Multiple Sclerosis HLA-DR3 Diabetes mellitus type 1 HLA-DR4 Arthritis (Rheumatoid) HLA-DR5 Anemia (Pernicious), Hashimoto's thyroiditis Educational Objective: Celiac disease is genetically predisposed by HLA-DQ2 or HLA-DQ8 HLA subtypes. References: First Aid 2014 page 199 Hunt KA, Zhernakova A, Turner G, et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet. 2008;40(4):395-402.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Celiac disease; HLA-DQ2; HLA-DQ8; HLA; diarrhea; chronic diarrhea; HLA;
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