Left ventricular noncompaction is associated with mutations in the mitochondrial genome |
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| Authors: | Sha Tang Anjan Batra Yu Zhang Eric S. Ebenroth Taosheng Huang |
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| Affiliation: | 1. Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow, Russian Federation;2. Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation;3. Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, Australia;4. School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia;5. Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow Region, Russian Federation;6. Department of Biophysics, Biological Faculty, Moscow State University, Moscow, Russian Federation;1. Institute of Genetics, Zhejiang University, Hangzhou, Zhejiang, China;2. Division of Human Genetics, Cincinnati Children''s Hospital Medical Center, Cincinnati, OH, USA;3. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China;4. Department of Laboratory Medicine, The Provincial People''s Hospital of Zhejiang, Hangzhou, Zhejiang, China;5. Division of Pathology and Pediatrics, Rady Children''s Hospital, University of California San Diego, San Diego, CA 92123, USA;1. Cardiovascular Section and Evans Department of Medicine, Boston University School of Medicine, Boston, MA, United States;2. Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, United States;3. BUSM Center for Human Genetics, Boston University School of Medicine, Boston, MA, United States;4. Boston University Medical Campus Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, United States;1. Unidad de Bioinformática, Institut Pasteur de Montevideo, Montevideo, Uruguay;2. Departamento de Genética, Facultad de Medicina, UDELAR, Uruguay;3. Departamento de Bioquímica, Facultad de Medicina, UDELAR, Uruguay;4. Instituto de Genética Médica, Montevideo, Uruguay;5. Center for Free Radical and Biomedical Research (CEINBIO), Montevideo, Uruguay;6. Departamento de Producción Animal y Pasturas, Facultad de Agronomía, UDELAR, Uruguay;7. Unidad de Biología Molecular, Institut Pasteur de Montevideo, Montevideo, Uruguay |
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| Abstract: | Left ventricular noncompaction (LVNC) is a genetically heterogeneous condition and several nuclear loci have been associated with the defect. However, they only account for a small percentage of patients. Existing evidences suggest that pathogenic mitochondrial DNA (mtDNA) mutations and consequent mitochondrial malfunction can be an important component in the etiology of LVNC. To investigate if mtDNA mutation can serve as a primary cause for LVNC, complete nucleotide sequences of mitochondrial genomes from 20 LVNC patients were determined by Illumina parallel sequencing technology and analyzed by MitoMaster. Substitutions of a highly conserved Met31 in ND1 caused by rare mitochondrial single nucleotide polymorphisms (mtSNP) A3397G and T3398C were identified from two LVNC patients. Previously, T3398C has been reported from another LVNC patient, indicating mutations in Met31 in ND1 and resultant defects in complex I can be associated with LVNC. Additionally, three mtSNPs in protein-coding genes, seven variants in rRNA genes, and two transitions in tRNA genes were unrelated to the haplogroup and infrequent in the general population, suggesting that these mtSNPs could also be pathogenic. Our study revealed some mtSNPs could represent pathogenic mutations, lead to compromised mitochondrial function, and be associated with LVNC. |
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