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.
Centro Dino Ferrari, Centro di eccellenza per le malattie neuro-degenerative, Dipartimento di Scienze Neurologiche, Università degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milano, Italy. neurogene@policlinico.mi.it
Marco
M
Crimi
Roberto
R
Del Bo
Sara
S
Galbiati
Monica
M
Sciacco
Andreina
A
Bordoni
Nereo
N
Bresolin
Giacomo Pietro
GP
Comi
D017668:Age of Onset; D004272:DNA, Mitochondrial / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008928:Mitochondria / Q000235:genetics; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
D004272:DNA, Mitochondrial