Abstract
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.
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References
Wallace DC, Brown MD, Lott MT : Mitochondrial DNA variation in human evolution and disease. Gene 1999; 238: 211–230, Review.
Zeviani M, Moraes CT, DiMauro S et al: Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 1998; 51: 1525–1532.
Macaulay V, Richards M, Hickey E et al: The emerging tree of west Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs. Am J Hum Genet 1999; 64: 232–249.
Sternberg D, Danan C, Lombes A et al: Exhaustive scanning approach to screen all the mitochondrial tRNA genes for mutations and its application to the investigation of 35 independent patients with mitochondrial disorders. Hum Mol Genet 1998; 7: 33–42.
Pulkes T, Sweeney MG, Hanna MG : Increased risk of stroke in patients with the A12308G polymorphism in mitochondria. Lancet 2000; 356: 2068–2069.
Grasso M, Diegoli M, Brega A, Campana C, Tavazzi L, Arbustini E : The mitochondrial DNA mutation T12297C affects a highly conserved nucleotide of tRNA(Leu(CUN)) and is associated with dilated cardiomyopathy. Eur J Hum Genet 2001; 9: 311–315.
Rose G, Passarino G, Carrieri G et al: Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians. Eur J Hum Genet 2001; 9: 701–707.
De Benedictis G, Carrieri G, Varcasia O, Bonafe M, Francesci C : Inherited variability of the mitochondrial genome and successful aging in humans. Ann NY Acad Sci 2000; 908: 208–218, Review.
Acknowledgements
Contract grant sponsor: the financial support of ‘Associazione amici del Centro Dino Ferrari’ is gratefully acknowledged. The Telethon ‘Bank of DNA, nerve and muscle tissues’ (GTF02008) was the source of the muscle for this study.
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Crimi, M., Bo, R., Galbiati, S. et al. Mitochondrial A12308G polymorphism affects clinical features in patients with single mtDNA macrodeletion. Eur J Hum Genet 11, 896–898 (2003). https://doi.org/10.1038/sj.ejhg.5201056
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DOI: https://doi.org/10.1038/sj.ejhg.5201056
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