WBR0118

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Musculoskeletal/Rheumatology, SubCategory::General Principles
Prompt	[[Prompt::A 5-year-old boy is brought to the physician by his parents for muscle weakness. When the child attempts to rise from the floor, he must use his hands and arms to “walk up” his own body. The boy undergoes genetic evaluation where portions of the DMD gene are subject to sanger sequencing. Which of the following mutations would indicate a frameshift mutation? (Assume that the first three leters represent the first codon) Reference Sequence: ACA GCT TAG GGC CAT]]
Answer A	AnswerA::ACA GCT TAA GGC CAT
Answer A Explanation	AnswerAExp::This is a nonsense mutation (inappropriate insertion of a stop codon)
Answer B	AnswerB::ACA GCT TAG GCC ATT
Answer B Explanation	AnswerBExp::The deletion of the second G in GGC causes a frameshift mutation.
Answer C	AnswerC::ACA CCT TAG GGC CAT
Answer C Explanation	AnswerCExp::This is a missense mutation
Answer D	AnswerD::ACA TAG GGC CAT TCC
Answer D Explanation	AnswerDExp::This sequence reflects the deletion of three nucleotides from the original sequence (GCT). Because the deleted region is a multiple of three, the reading frame of the sequence is preserved.
Answer E	AnswerE::ACA GCT GCT TAG GGC
Answer E Explanation	AnswerEExp::This sequence reflects the insertion of three nucleotides into the original sequence (GCT). Because the inserted region is a multiple of three, the reading frame of the sequence is preserved.
Right Answer	RightAnswer::B
Explanation	[[Explanation::The patient in this vignette is suffering from Duchenne Muscular Dystrophy (DMD). DMD is caused by mutations in the DMD gene which codes for the protein Dystrophin. The mutations associated with this disease often represent the mutations whose effects are most deleterious to the structure of the final gene product. Thus, frameshift and nonsense mutations more commonly cause Duchenne Muscular Dystrophy than missense mutations. Frameshift mutations refer to the insertion or deletion of nucleotides which shift the reading frame of the mRNA and cause amino acids or stop codons not specified by the original sequence to be read. Educational Objective: A frameshift is a genetic mutation caused by indels (insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. References: First Aid 2012 page 67.]]
Approved	Approved::Yes
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