WBR0116

Author	[[PageAuthor::Mahmoud Sakr (Reviewed by Will J Gibson, Rim Halaby, M.D. [1], and Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Gastrointestinal
Prompt	[[Prompt::A 33-year-old Caucasian female presents with complaints of diarrhea and foul-smelling bulky stools for the past 3 weeks. She previously 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 blood pressure is 120/80 mmHg, heart rate is 70/min, and temperature is 36.8 °C (98.24 °F). Serological testing reveals elevated levels of tissue transglutaminase IgA antibodies. Which of the following gene mutations most likely predisposed this patient to develop his condition?]]
Answer A	AnswerA::''HLA-DQ2'' gene
Answer A Explanation	[[AnswerAExp::This patient in the vignette suffers from celiac disease or gluten-sensitive enteropathy, which is associated with mutations of HLA-DQ2 or HLA-DQ8 subtypes.]]
Answer B	AnswerB::''HLA-A3'' gene
Answer B Explanation	AnswerBExp::HLA-A3 gene mutation is associated with development of Hemochromatosis.
Answer C	AnswerC::''HLA-DR2'' gene
Answer C Explanation	[[AnswerCExp::The HLA-DR2 variant is associated with inflammatory bowel disease.]]
Answer D	AnswerD::''HLA-DR5'' gene
Answer D Explanation	AnswerDExp::HLA-DR5 is associated with pernicious anemia and Hashimoto's thyroiditis
Answer E	AnswerE::''HLA-DR3'' gene
Answer E Explanation	AnswerEExp::HLA-DR3 is associated with development of diabetes mellitus type 1, SLE, and Graves disease.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Celiac disease is an autoimmune disease of the small intestine that occurs among genetically predisposed individuals of all ages. The onset of symptoms is typically during late childhood or early adulthood. Symptoms include abdominal pain and discomfort, chronic diarrhea, failure to thrive in children, anemia and fatigue. Abdominal symptoms may be absent and symptoms in other organ systems could also be present. IgA antibodies against tissue transglutaminase are present almost all patients with celiac disease. Serology for anti-tTG IgA antibodies is a very sensitive (99%) and specific (>90%) for identifying celiac disease. Other serological tests, anti-endomysium, anti-gliadin, and anti-reticulin may also be used, but are less sensitive and less specific. The greatest risk factor for celiac disease is a positive family history, followed by a mutation of HLA-DQ2. Celiac disease is associated with mutations of both HLA-DQ2 or HLA-DQ8 subtypes. While these HLA subtypes are present in approximately 30% of individuals of European descent, only 1% of the population develops celiac disease. Common HLA subtypes and their associated diseases are shown in the table below. HLA Subtype Associated disease HLA-A3 Hemochromatosis HLA-B27 Ankylosing spondylitis, psoriatic arthritis, arthritis of inflammatory bowel disease, and reactive arthritis HLA-DQ2 and HLD-DQ8 Celiac disease HLA-DR2 Multiple sclerosis, hay fever, SLE, and Goodpasture syndrome HLA-DR3 Diabetes mellitus type I, SLE, and Graves disease HLA-DR4 Rheumatoid arthritis, diabetes mellitus type I HLA-DR5 Pernicious anemia, Hashimoto's thyroiditis Educational Objective: Celiac disease is associated with mutatioans of HLA subtypes HLA-DQ2 or HLA-DQ8. References: 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. First Aid 2014 page 199]]
Approved	Approved::Yes
Keyword	WBRKeyword::Celiac disease, WBRKeyword::Autoimmune, WBRKeyword::Diarrhea, WBRKeyword::Chronic diarrhea, WBRKeyword::Chronic, WBRKeyword::Abdominal pain, WBRKeyword::Pain, WBRKeyword::Abdominal, WBRKeyword::HLA, WBRKeyword::Subtype, WBRKeyword::HLA subtype, WBRKeyword::HLA-DQ, WBRKeyword::HLA-DQ2, WBRKeyword::HLA-DQ8, WBRKeyword::HLA DQ2, WBRKeyword::HLA DQ8, WBRKeyword::Genetic mutation, WBRKeyword::Gene, WBRKeyword::Mutation, WBRKeyword::Predispose, WBRKeyword::Predisposition, WBRKeyword::Gluten, WBRKeyword::Insensitive, WBRKeyword::Insensitivity
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