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Mitochondrial mutations in patients with congenital heart defects by next generation sequencing technology

Published online by Cambridge University Press:  10 June 2014

Neslihan Abaci ,
Muzaffer Arıkan ,
Türkan Tansel ,
Nazlı Sahin ,
Aris Cakiris ,
Ferda Pacal ,
Sema Sırma Ekmekci ,
Emre Gök  and
Duran Üstek
Neslihan Abaci
Affiliation:
Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey
Muzaffer Arıkan
Affiliation:
Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey
Türkan Tansel
Affiliation:
Department of Cardiovascular Surgery, Istanbul Medical Faculty, Istanbul University, Turkey
Nazlı Sahin
Affiliation:
Department of Cardiovascular Surgery, Istanbul Medical Faculty, Istanbul University, Turkey
Aris Cakiris
Affiliation:
Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey
Ferda Pacal
Affiliation:
Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey
Sema Sırma Ekmekci
Affiliation:
Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey
Emre Gök
Affiliation:
Department of Cardiovascular Surgery, Istanbul Medical Faculty, Istanbul University, Turkey
Duran Üstek*
Affiliation:
Department of Genetics, Institute for Experimental Medicine, Istanbul University, Turkey
*
Correspondence to: D. Üstek, Vakif Gureba c. I.U. DETAE Genetik AD, Şehremini, İstanbul. Tel: +90 2124142000x33316; Fax:+90 543 210 10 79; E-mail: [email protected]
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Abstract

It has been shown that mitochondrial deoxyribo nucleic acid mutations may play an important role in the development of cardiomyopathy, and various types of cardiomyopathy can be attributed to disturbed mitochondrial oxidative energy metabolism. Several studies have described many mutations in mitochondrial genes encoding for subunits of respiratory chain complexes. Thus, recent studies confirm that pathologic mitochondrial deoxyribo nucleic acid mutations are a major reason of diseases and determining them by next-generation sequencing will improve our understanding of dysregulation of heart development. To analyse mitochondrial deoxyribo nucleic acid mutations, the entire mitochondrial deoxyribo nucleic acid was amplified in two overlapping polymerase chain reaction fragments from the cardiac tissue of the 22 patients with congenital heart disease, undergoing cardiac surgery. Mitochondrial deoxyribo nucleic acid was deep sequenced by next-generation sequencing. A total of 13 novel mitochondrial deoxyribo nucleic acid mutations were identified in nine patients. Of the patients, three have novel mutations together with reported cardiomyopathy mutations. In all, 65 mutations were found, and 13 of them were unreported. This study represents the most comprehensive mitochondrial deoxyribo nucleic acid mutational analysis in patients with congenital heart disease.

Keywords

Congenital heart defectsnext-generation sequencingmitochondrial mutations
Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Supplement 4 , April 2015 , pp. 705 - 711
Copyright
© Cambridge University Press 2014 

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References

1. Maron, BJ, Towbin, JA, Thiene, G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113: 1807–1816.Google Scholar
2. Anderson, S, Bankier, AT, Barrell, BG, et al. Sequence and organization of the human mitochondrial genome. Nature 1981; 290: 457–465.Google Scholar
3. Giles, RE, Blanc, H, Cann, HM, Wallace, DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A 1980; 77: 6715–6719.Google Scholar
4. Cree, LM, Samuels, DC, Chinnery, PF. The inheritance of pathogenic mitochondrial DNA mutations. Biochim Biophys Acta 2009; 1792: 1097–1102.CrossRefGoogle ScholarPubMed
5. Sanger, F, Nicklen, S, Coulson, AR. DNA sequencing with chainterminating inhibitors. Proc Natl Acad Sci U S A 1977; 74: 5463–5467.Google Scholar
6. Voelkerding, KV, Dames, SA, Durtschi, JD. Next-generation sequencing:from basic research to diagnostics. Clin Chem 2009; 55: 641–658.CrossRefGoogle ScholarPubMed
7. Meyer, M, Briggs, AW, Maricic, T, et al. From micrograms to picograms: quantitative polymerase chain reaction reduces the material demands of high-throughput sequencing. Nucleic Acids Res 2008; 36.Google Scholar
8. Green, RE, Malaspinas, AS, Krause, J, et al. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell 2008; 134: 416–426.Google Scholar
9. Zaragoza, MV, Fass, J, Diegoli, M, Lin, D, Arbustini, E. Mitochondrial DNA variant discovery and evaluation in human cardiomyopathies through next-generation sequencing. PLoS One 2010; 5: e12295.Google Scholar
10. Gunnarsdóttir, ED, Li, M, Bauchet, M, Finstermeier, K, Stoneking, M. High-throughput sequencing of complete human mitochondrial DNA genomes from the Philippines. Genome Res 2011; 21: 1–11.Google Scholar
11. Johns, DR, Neufeld, MJ. Cytochrome c oxidase mutations in Leber hereditary optic neuropathy. Biochem Biophys Res Commun 1993; 196: 810–815.Google Scholar
12. Boles, RG, Zaki, EA, Lavenbarg, T, et al. Are pediatric and adult-onset cyclic vomiting syndrome (CVS) biologically different conditions? Relationship of adult-onset CVS with the migraine and pediatric CVS-associated common mitochondrial DNA polymorphisms 16519T and 3010A. Neurogastroenterol Motil 2009; 21: 936–e72.Google Scholar
13. Brown, MD, Torroni, A, Reckord, CL, Wallace, DC. Phylogenetic analysis of Leber’s hereditary optic neuropathy mitochondrial DNA’s indicates multiple independent occurrences of the common mutations. Hum Mutat 1995; 6: 311–325.Google Scholar
14. Canter, JA, Kallianpur, AR, Parl, FF, Millikan, RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005; 65: 8028–8033.Google Scholar
15. Shin, WS, Tanaka, M, Suzuki, J, Hemmi, C, Toyo-Oka, T. A novel homoplasmic mutation in mitochondrial DNA with a single evolutionary origin as a risk factor for cardiomyopathy. Am J Hum Genet 2000; 67: 1617–1620.Google Scholar
16. Lu, J, Qian, Y, Li, Z, et al. Mitochondrial haplotypes may modulate the phenotypic manifestation of the deafness-associated 12S rRNA 1555A>G mutation. Mitochondrion 2010; 10: 69–81.Google Scholar
17. Howell, N, Kubacka, I, Halvorson, S, Mackey, D. Leber’s hereditary optic neuropathy: the etiological role of a mutation in the mitochondrial cytochrome b gene. Genetics 1993; 133: 133–136.Google Scholar
18. Rollins, B, Martin, MV, Sequeira, PA, et al. Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder. PLoS One 2009; 4: e4913.Google Scholar
19. Zifa, E, Theotokis, P, Kaminari, A, et al. A novel G3337A mitochondrial ND1 mutation related to cardiomyopathy co-segregates with tRNALeu(CUN) A12308G and tRNAThr C15946T mutations. Mitochondrion 2008; 8: 229–236.CrossRefGoogle ScholarPubMed
20. Merante, F, Tein, I, Benson, L, Robinson, BH. Maternally inherited hypertrophic cardiomyopathy due to a novel T-to-C transition at nucleotide 9997 in the mitochondrial tRNA (glycine) gene. Am J Hum Genet 1994; 55: 437–446.Google Scholar
21. Tang, S, Batra, A, Zhang, Y, Ebenroth, ES, Huang, T. Left ventricular noncompaction is associated with mutations in the mitochondrial genome. Mitochondrion 2010; 10: 350–357.Google Scholar
22. Young, WY, Zhao, L, Qian, Y, et al. Variants in mitochondrial tRNAGlu, tRNAArg, and tRNAThr may influence the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in three Han Chinese families with hearing loss. Am J Med Genet 2006; 140: 2188–2219.Google Scholar
23. Neubauer, S. The failing heart: an engine out of fuel. N Engl J Med 2007; 356: 1140 –1151.Google Scholar
24. Azaragoza, MV, Brandon, MC, Diegoli, M, Arbustini, E, Wallace, DC. Mitochondrial cardiomyopathies: how to identify candidate pathogenic mutations by mitochondrial DNA sequencing, MITOMASTER and phylogeny. Eur J Hum Genet 2011; 19: 200–207; Epub 2010 Oct 27.Google Scholar
25. DiMauro, S, Schon, EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003; 348: 2656–2668.Google Scholar
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