Review Question - QID 214433

A geneticist studies a family of patients who have a rare disease that causes early onset dementia in an autosomal dominant fashion. She finds that patients with the disease have a defective protease that does not catalyze normal degradation of certain lipid byproducts. Western blot analysis of this protein shows that the mutant allele produces a variant that is 10 kilodaltons larger than the wild type protein. Further structural studies show that an extra loop of unfolded amino acids is incorporated into the middle of the protein near the active site and blocks proper substrate binding. She sequences the wildtype and mutant genes and finds that there is a specific mutation responsible for the disease. Which of the following mutations is most likely seen in this family?