View source for WBR0118

{{WBRQuestion
|QuestionAuthor=William J Gibson
|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
|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 most deleterious mutations which sometimes cause this disease are frameshift mutations.  These 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.

|AnswerA=ACA GCT TAA GGC CAT
|AnswerAExp='''Incorrect''' – This is a nonsense mutation (inappropriate insertion of a stop codon)
|AnswerB=ACA GCT TAG GCC ATT
|AnswerBExp='''Correct''' – The deletion of the second G in GGC causes a frameshift mutation.
|AnswerC=ACA CCT TAG GGC CAT
|AnswerCExp='''Incorrect''' – This is a missense mutation
|AnswerD=ACA TAG GGC CAT TCC
|AnswerDExp='''Incorrect''' – 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.
|AnswerE=ACA GCT GCT TAG GGC
|AnswerEExp='''Incorrect''' – 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.
|RightAnswer=B
|Approved=Yes
}}