Chapter 18, Problem 33P

Recall that Leber congenital amaurosis (LCA), a form of congenital blindness in humans, can be caused by homozygosity for recessive mutations in the RPE65 gene. Recently, a rare dominant mutation in RPE65 has been implicated as one cause of an eye disease called retinitis pigmentosa, which is characterized by retinal degeneration that can progress to blindness. The dominant RPE65 mutation is a missense mutation causing amino acid 447 in the polypeptide to change from Asp to Glu. Little is known about the nature of the mutant protein.

a.	Do you think that the dominant allele is more likely a loss-of-function or a gain-of-function mutation? Explain.
b.	As described in this chapter, gene therapy for LCA has been at least partially successful. Do you think that the same kind of gene therapy can be used for patients with retinitis pigmentosa caused by the dominant mutant allele of RPE65? Explain.