Chapter 15, Problem 27P

Leigh syndrome is characterized by psychomotor regression: that is, the progressive loss of mental and movement abilities. Patients also suffer from lactic acidosis, a condition in which mitochondrial respiration is deficient, so their tissues metabolize glucose anaerobically, leading to the buildup of lactate. Some patients with Leigh syndrome have a mutation in the mitochondrial gene MT-CO3, which encodes a subunit of the electron transport complex cytochrome c oxidase. Other patients diagnosed with Leigh syndrome have a loss-of-function mutation in the nuclear gene SURF1, which encodes a factor needed for the assembly of this same enzyme complex.

a.	How can the same symptoms result from mutations in a mitochondrial gene and from mutations in a nuclear gene?
b.	Does the pedigree shown provide enough evidence to discriminate between the possibilities that Page 546 Leigh syndrome in this family is due to a mutation in a mitochondrial gene or in a nuclear gene? (Remember that many diseases, whether resulting from nuclear or mtDNA mutations, are incompletely penetrant or show variable expressivity.)
c.	In what practical way would it be helpful to members of this family to discriminate between these two possible modes of inheritance?