WBR0108
| Author | PageAuthor::William J Gibson |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Cardiology |
| Prompt | [[Prompt::A 32 year old woman is brought to the emergency room after being involved in a motor vehicle accident. She complains of the sudden onset of a tearing chest pain which radiates between the scapula. Her pulse is 110, respiratory rate is 20. The physician notes that the patient is unusually tall and lean, with very long fingers. Chest X Ray reveals a widened mediastinum. If a genetic defect had predisposed the patient to her current condition, which of the following is the most likely causal gene?]] |
| Answer A | AnswerA::COLA1 |
| Answer A Explanation | AnswerAExp::Incorrect - Mutation in COLA1 the gene coding for collagen type 1 is responsible for osteogenesis imperfecta |
| Answer B | AnswerB::COLA3 |
| Answer B Explanation | AnswerBExp::Incorrect - Mutation of COLA3, the gene coding for collagen type 3 is responsible for the hypermobility subtype of Ehlers-Danlos syndrome. |
| Answer C | AnswerC::TGFBR2 |
| Answer C Explanation | AnswerCExp::Incorrect - Mutation in TGFBR2 causes Loeys-Dietz Syndrome, which is highly similar to Marfan syndrome but much rarer. |
| Answer D | AnswerD::FBN1 |
| Answer D Explanation | AnswerDExp::Correct - Mutation of the FBN1 gene, which codes for the extracellular matrix protein fibrillin is responsible for Marfan syndrome. |
| Answer E | AnswerE::FGFR3 |
| Answer E Explanation | AnswerEExp::Incorrect - Mutation of the FGFR3 gene is responsible for achondroplasia, the most common cause of dwarfism. |
| Right Answer | RightAnswer::D |
| Explanation | [[Explanation::The patient in this vignette is suffering from a thoracic aortic dissection secondary to Marfan Syndrome. Marfan syndrome is a genetic disorder of the connective tissue. People with Marfan tend to be unusually tall, with long limbs and long, thin fingers. Marfan syndrome has a range of expressions, from mild to severe. The most serious complications are defects of the heart valves and aorta. Marfan syndrome is a dominant genetic trait, meaning that people who inherit only one copy of the Marfan FBN1 gene from either parent will develop Marfan syndrome.
The syndrome is carried by the gene FBN1, which encodes the connective protein fibrillin-1. Fibrillin-1 protein is essential for the proper formation of the extracellular matrix, including the biogenesis and maintenance of elastic fibers. In addition to being a connective protein that forms the structural support for tissues outside the cell, the normal fibrillin-1 protein binds to another protein,transforming growth factor beta (TGF-β). TGF-β has deleterious effects on vascular smooth muscle development and the integrity of the extracellular matrix. Fibrillin-1 directly binds a latent form of TGFβ, keeping it sequestered and unable to exert its biological activity. Researchers now believe, secondary to mutated fibrillin, excessive TGF-β at the lungs, heart valves, and aorta weakens the tissues and causes the features of Marfan syndrome. References: First Aid page 90. Tags: #Genetics #Cardiology |
| Approved | Approved::Yes |
| Keyword | |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |