WBR0368

Author	[[PageAuthor::Mahmoud Sakr M.D. (Reviewed by Serge Korjian M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 20-year-old man presents to the neurology clinic for left foot weakness and gradual loss sensation in the both lower extremities. His symptoms have been progressive over the past 2 years. On physical examination, the physician notes significant pes cavus with left foot drop, lower extremity weakness and muscle wasting giving the legs an inverted champagne bottle appearance. The patient explains that several of his family members have had the same condition. A mutation in which of the following gene is likely to be responsible for this patient's condition?]]
Answer A	AnswerA::''CMT'' gene
Answer A Explanation	AnswerAExp::Charcot–Marie–Tooth (CMT) disease is caused by mutations in one of several ''CMT'' genes involved in the structure and function of either the peripheral nerve axon or the myelin sheath.
Answer B	AnswerB::''FXN'' gene
Answer B Explanation	AnswerBExp::Friedreich's ataxia (FRDA) is caused by ''FXN'' gene mutation that results in reduced expression of frataxin protein.
Answer C	AnswerC::DUX4 gene
Answer C Explanation	AnswerCExp::Facioscapulohumeral muscular dystrophy is caused by ''DUX4'' gene mutation.
Answer D	AnswerD::''Dystrophin'' gene
Answer D Explanation	AnswerDExp::Duchenne muscular dystrophy (DMD) is caused by ''Dystrophin'' gene frameshift mutation.
Answer E	AnswerE::''DYSF'' gene
Answer E Explanation	[[AnswerEExp::Distal muscular dystrophy is caused by a mutation in the DYSF. The disease is characterized by relatively late-onset of symptoms (20-60 years of age), which include weakness and wasting of muscles of the hands, forearms, and lower legs. It is usually progressive but not life-threatening.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::Charcot–Marie–Tooth (CMT) disease is a common inherited disorder occurring in approximately 1 in 2500 people in the United States. CMT is caused by mutations in CMT genes involved in the structure and function of either the peripheral nerve axon or the myelin sheath. This leads to slowly progressive degeneration of peripheral motor and sensory nerves. Patients with CMT typically present in late childhood or early adulthood with sensorimotor neuropathy. Loss of touch sensation in the feet, ankles and legs, as well as in the hands, wrists and arms is characteristic in various types of the disease. Sensory and proprioceptive nerves in the hands and feet are often damaged, while pain nerves are left intact. Wasting of muscle tissue of the lower parts of the legs may give rise to a "stork leg" or "inverted champagne bottle" appearance. Educational Objective: Charcot–Marie–Tooth (CMT) disease is caused by mutations in CMT genes involved in the structure and function of either the peripheral nerve axon or the myelin sheath. References: Bird TD. Charcot-Marie-Tooth Neuropathy Type 1. 1998 Aug 31 [Updated 2015 Mar 26]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1205/ First Aid 2015 page 489.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Charcot-Marie-Tooth, WBRKeyword::CMT, WBRKeyword::Neuropathy, WBRKeyword::Mutation
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::