Mitochondrial A12308G polymorphism affects clinical features in patients with single mtDNA macrodeletion

Mitochondrial (mt)DNA alterations cause cellular energy failure and respiratory chain dysfunction. Single large-scale rearrangements represent the most common mtDNA mutations and are responsible for very variable clinical manifestations. Here, we show an increased frequency of the A12308G substitution, a common polymorphism used to define the European mtDNA haplogroup U, in mitochondrial patients carrying mtDNA single macrodeletion. In this group of patients, A12308G substitution is associated with a higher relative risk of developing pigmentary retinal degeneration, short stature, dysphasia-dysarthria and cardiac conduction defects. MtDNA haplotype might modulate the clinical expression of mitochondrial encephalomyopathies due to mtDNA macrodeletions.