Chapter 14, Problem 24P

Kearns-Sayre syndrome (KSS), Pearson syndrome, and progressive external opthalmoplegia (PEO) are rare diseases in which up to 7.6 kb of the mitochondrial genome is deleted. KSS affects the central nervous system, skeletal muscle, and heart; patients often die in young adulthood. Pearson syndrome is characterized by severe anemia and pancreatic dysfunction. The condition is usually fatal during infancy, but the few survivors often develop the symptoms of KSS. PEO patients have ptosis (drooping eyelids) and weakness in the limbs, but they have normal life spans.

a.	How can you explain the variation in tissues affected and severity of symptoms in patients with these three conditions, given that they all bear large deletions of mtDNA? (Assume that the size of the deletion does not contribute to phenotypic differences.)
b.	What can you conclude from these diseases about the location of the origin of replication for mtDNA?
c.	Although these syndromes are due to mtDNA deletions, they are not usually maternally inherited but instead arise as a new mutation in an individual. For example, mothers with PEO usually do not transmit this trait to their offspring. Propose an explanation for this surprising finding.