WBR1020

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	USMLE Step 1
Main Category	Genetics
Sub Category	Musculoskeletal/Rheumatology
Prompt	A 2-year-old boy is brought to the physician's office for muscle weakness. The mother explains that the boy walks differently than his siblings his age, and when he tries to stand up from a squatting position, he walks up his own body using both hands and feet. The physician suspects the patient has an X-linked recessive congenital disease. Both parents deny any family history of similar symptoms. Which of the following genetic mechanisms best explains the patient's underlying condition?
Answer A	A CGG expansion that results in the disruption of the promoter of the dystrophin gene
Answer A Explanation	A CGG expansion results in Fragile X syndrome due to an X-linked defect that affects methylation and expression of the FMR1 gene. Fragile X syndrome is not caused by mutation in the dystrophin gene.
Answer B	A point mutation in the dystrophin gene
Answer B Explanation	DMD results from a frameshift mutation, not from a point mutation.
Answer C	A translocation that results in the disruption of the dystrophin gene
Answer C Explanation	A frameshift mutation, not a translocation, causes a deletion in the dystrophin gene.
Answer D	A recombination event in the dystrophin gene that gives rise to a frameshift mutation
Answer D Explanation	Duchenne Muscular Dystrophy (DMD) is an X-linked frameshift mutation caused by the deletion of segments of the dystrophin gene.
Answer E	A CTG expansion that results in the disruption of the dystrophin gene
Answer E Explanation	A CTG expansion causes myotonic dystrophy. it is not associated with disruption of the dystrophin gene.
Right Answer	D
Explanation	Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder caused by frameshift mutation due to deletion of segments of the dystrophin gene. The mutation results in the acceleration of muscle breakdown. Clinical manifestations of DMD typically start at early age before 5 years of age and include proximal muscle weakness, calf pseudohypertrophy, and positive gower's sign (patients walk up their own body and use both hands and feet to stand up from a squatting position). Educational Objective: Duchenne Muscular Dystrophy (DMD) is an X-linked frameshift mutation caused by the deletion of segments of the dystrophin gene. References: First Aid 2015 page 84.
Approved	Yes
Keyword	Duchenne muscular dystrophy, DMD, Muscle weakness, Mutation, Frameshift mutation
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