Severity of cardiomyopathy associated with adenine nucleotide translocator-1 deficiency correlates with mtDNA haplogroup
| Autor: | Peng Li, Richard I. Kelley, Julia Platt, Navneet Narula, Mariella Simon, Vincent Procaccio, Jagat Narula, Kevin A. Strauss, Lauren DuBiner, Erik G. Puffenberger, Michael V. Zaragoza, Partho P. Sengupta, D. Holmes Morton, Xilma R. Ortiz-Gonzalez, Douglas C. Wallace, Sandra Dreike |
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| Přispěvatelé: | Franklin and Marshall College, University of California [Irvine] (UCI), University of California, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Standford University, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), University of Pennsylvania [Philadelphia] |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Mitochondrial DNA medicine.medical_specialty Adolescent Mitochondrial disease [SDV]Life Sciences [q-bio] Cardiomyopathy Biology DNA Mitochondrial Haplogroup 03 medical and health sciences 0302 clinical medicine Adenine Nucleotide Translocator 1 Adenine nucleotide Internal medicine medicine Medicine and Health Sciences Humans 030304 developmental biology 0303 health sciences Multidisciplinary Myocardium Haplotype Homozygote Biological Sciences medicine.disease Molecular biology 3. Good health Pedigree Endocrinology Haplotypes Mutation Disease Progression Female Cardiomyopathies 030217 neurology & neurosurgery Human mitochondrial DNA haplogroup |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2013, 110 (9), pp.3453-8. ⟨10.1073/pnas.1300690110⟩ Strauss, Kevin A.; DuBiner, Lauren; Simon, Mariella; Zaragoza, Michael; Sengupta, Partho P.; Li, Peng; et al.(2013). Severity of cardiomyopathy associated with adenine nucleotide translocator-1 deficiency correlates with mtDNA haplogroup. Proceedings of the National Academy of Sciences of the United States of America, 110(9), 3453-3458. UC Irvine: Institute for Clinical and Translational Science. Retrieved from: http://www.escholarship.org/uc/item/4n40k6f1 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1300690110⟩ |
| Popis: | Mutations of both nuclear and mitochondrial DNA (mtDNA)–encoded mitochondrial proteins can cause cardiomyopathy associated with mitochondrial dysfunction. Hence, the cardiac phenotype of nuclear DNA mitochondrial mutations might be modulated by mtDNA variation. We studied a 13-generation Mennonite pedigree with autosomal recessive myopathy and cardiomyopathy due to an SLC25A4 frameshift null mutation (c.523delC, p.Q175RfsX38), which codes for the heart-muscle isoform of the adenine nucleotide translocator–1. Ten homozygous null (adenine nucleotide translocator–1 −/− ) patients monitored over a median of 6 years had a phenotype of progressive myocardial thickening, hyperalaninemia, lactic acidosis, exercise intolerance, and persistent adrenergic activation. Electrocardiography and echocardiography with velocity vector imaging revealed abnormal contractile mechanics, myocardial repolarization abnormalities, and impaired left ventricular relaxation. End-stage heart disease was characterized by massive, symmetric, concentric cardiac hypertrophy; widespread cardiomyocyte degeneration; overabundant and structurally abnormal mitochondria; extensive subendocardial interstitial fibrosis; and marked hypertrophy of arteriolar smooth muscle. Substantial variability in the progression and severity of heart disease segregated with maternal lineage, and sequencing of mtDNA from five maternal lineages revealed two major European haplogroups, U and H. Patients with the haplogroup U mtDNAs had more rapid and severe cardiomyopathy than those with haplogroup H. |
| Databáze: | OpenAIRE |
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