USMLE Step 1 Question 398

Question:

A patient with a rare hereditary tumor syndrome is found to have a mutation in a gene on chromosome 16. When researchers clone the gene, they find that the mutant gene generates a protein that is 428 amino acid residues long. The wild type of the gene normally produces a protein 683 amino acid residues long. The researchers note that the mRNA generated from the mutant gene is significantly longer than the wild type. In which part of the gene did the mutation likely take place?

Correct Answer: C.  Splice Site

This patient has a splice site mutation. The splice site is located within the intron. The removal of the splice site causes the mutant gene to retain an intron and results in the production of an abberant protein. In this case, the added intron contains a stop codon and causes the translation of the protein to terminate at codon 428. This explains why the mRNA is longer than normal but the protein is shorter.

A mutation in the enhancer or the promoter may cause weaker expression of the mutant protein but would not affect its length.

A mutation in one of the exons may create a stop codon which causes translation to terminate early, but would not create a longer mRNA.

A mutation in the start codon would cause the mutant protein not to be expressed at all.