Abstract
Mitochondrial DNA (mtDNA) mutations have been causally linked with cardiomyopathies, both dilated (DCM) and hypertrophic. We identified the T12297C mutation in the mtDNA-tRNALeu(CUN) of a 36-year-old male patient diagnosed with DCM. The mutation was heteroplasmic, with high amount (88%) of mutant DNA in the myocardium, and was absent in normal (n=120) and disease (n=150) controls. It affects a highly conserved nucleotide (adjacent to the anticodon triplet) that allows the phospho-ribose backbone to turn and form the loop. The potential pathological role of T12297C mutation is further supported by its recent identification in another unrelated Italian family with DCM associated with endocardial fibroelastosis. In the variable loop of the same tRNA, our patient also carried the A12308G transition that is debated as pathological mutation or neutral polymorphism in progressive external ophthalmoplegia: the two defects could exert a synergistic effect on the tRNA structure and function. The endomyocardial biopsy study showed abnormal ring-like mitochondria and occasional cytochrome c oxydase negative myocytes. Overall, the heteroplasmy, the highly conserved position of the mutated nucleotide, the absence of the mutation in large series of diseased and normal controls, and the cardiac mitochondrial changes support a causative link of the mutation with the disease.
| Original language | English |
|---|---|
| Pages (from-to) | 311-315 |
| Number of pages | 5 |
| Journal | European Journal of Human Genetics |
| Volume | 9 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2001 |
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Keywords
- Dilated cardiomyopathy
- Mitochondrial DNA
- TRNAC
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
The mitochondrial DNA mutation T12297C affects a highly conserved nucleotide of tRNALeu(CUN) and is associated with dilated cardiomyopathy. / Grasso, Maurizia; Diegoli, Marta; Brega, Agnese; Campana, Carlo; Tavazzi, Luigi; Arbustini, Eloisa.
In: European Journal of Human Genetics, Vol. 9, No. 4, 2001, p. 311-315.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The mitochondrial DNA mutation T12297C affects a highly conserved nucleotide of tRNALeu(CUN) and is associated with dilated cardiomyopathy
AU - Grasso, Maurizia
AU - Diegoli, Marta
AU - Brega, Agnese
AU - Campana, Carlo
AU - Tavazzi, Luigi
AU - Arbustini, Eloisa
PY - 2001
Y1 - 2001
N2 - Mitochondrial DNA (mtDNA) mutations have been causally linked with cardiomyopathies, both dilated (DCM) and hypertrophic. We identified the T12297C mutation in the mtDNA-tRNALeu(CUN) of a 36-year-old male patient diagnosed with DCM. The mutation was heteroplasmic, with high amount (88%) of mutant DNA in the myocardium, and was absent in normal (n=120) and disease (n=150) controls. It affects a highly conserved nucleotide (adjacent to the anticodon triplet) that allows the phospho-ribose backbone to turn and form the loop. The potential pathological role of T12297C mutation is further supported by its recent identification in another unrelated Italian family with DCM associated with endocardial fibroelastosis. In the variable loop of the same tRNA, our patient also carried the A12308G transition that is debated as pathological mutation or neutral polymorphism in progressive external ophthalmoplegia: the two defects could exert a synergistic effect on the tRNA structure and function. The endomyocardial biopsy study showed abnormal ring-like mitochondria and occasional cytochrome c oxydase negative myocytes. Overall, the heteroplasmy, the highly conserved position of the mutated nucleotide, the absence of the mutation in large series of diseased and normal controls, and the cardiac mitochondrial changes support a causative link of the mutation with the disease.
AB - Mitochondrial DNA (mtDNA) mutations have been causally linked with cardiomyopathies, both dilated (DCM) and hypertrophic. We identified the T12297C mutation in the mtDNA-tRNALeu(CUN) of a 36-year-old male patient diagnosed with DCM. The mutation was heteroplasmic, with high amount (88%) of mutant DNA in the myocardium, and was absent in normal (n=120) and disease (n=150) controls. It affects a highly conserved nucleotide (adjacent to the anticodon triplet) that allows the phospho-ribose backbone to turn and form the loop. The potential pathological role of T12297C mutation is further supported by its recent identification in another unrelated Italian family with DCM associated with endocardial fibroelastosis. In the variable loop of the same tRNA, our patient also carried the A12308G transition that is debated as pathological mutation or neutral polymorphism in progressive external ophthalmoplegia: the two defects could exert a synergistic effect on the tRNA structure and function. The endomyocardial biopsy study showed abnormal ring-like mitochondria and occasional cytochrome c oxydase negative myocytes. Overall, the heteroplasmy, the highly conserved position of the mutated nucleotide, the absence of the mutation in large series of diseased and normal controls, and the cardiac mitochondrial changes support a causative link of the mutation with the disease.
KW - Dilated cardiomyopathy
KW - Mitochondrial DNA
KW - TRNAC
UR - http://www.scopus.com/inward/record.url?scp=0035058912&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035058912&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5200622
DO - 10.1038/sj.ejhg.5200622
M3 - Article
C2 - 11313776
AN - SCOPUS:0035058912
VL - 9
SP - 311
EP - 315
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 4
ER -