Document Detail


The complete sequence of mtDNA genes in idiopathic dilated cardiomyopathy shows novel missense and tRNA mutations.
MedLine Citation:
PMID:  11145757     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Previous studies have shown that mitochondrial DNA (mtDNA) mutations are often present in patients with myocardial dysfunction. We sought to assess the prevalence and significance of heart mtDNA sequence changes in patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: DNA sequence of all the transfer ribonucleic acid (tRNA), ribosomal RNA (rRNA), and structural genes in cardiac mtDNA of 28 patients with DCM was determined and compared with a control group that had no evidence of heart disease. An increased number of point mutations were found in DCM cardiac mtDNA when compared with controls. Both novel and previously reported mutations were found in mitochondrial tRNA and structural genes. One of these mutations was heteroplasmic and resulted in changing a highly conserved nucleotide in tRNAArg. Novel, heteroplasmic mtDNA mutations (n = 4) specifying changes in moderate to highly conserved amino acid residues were found in COII, COIII, ND5, and cytb. These novel mtDNA mutations were found only in patients with severe reduction in mitochondrial enzyme activities. CONCLUSIONS: Our results indicate that a high incidence of mtDNA nucleotide sequence changes in both tRNA and structural genes are present in DCM. Five heteroplasmic mutations were detected that both changed evolutionarily conserved residues (which may impair the function of proteins or tRNAs) and were associated with specific enzymatic defects. These mutations could play an important role in the pathogenesis of cardiomyopathy.
Authors:
J Marin-Garcia; M J Goldenthal; R Ananthakrishnan; M E Pierpont
Related Documents :
8662207 - Physical and genetic map of the mitochondrial genome of cryphonectria parasitica ep155.
20590837 - Mitochondrial haplogroups associated with lifestyle-related diseases and longevity in t...
8534127 - Photoageing-associated mitochondrial dna length mutations in human skin.
12089377 - Mitochondrial dna mutations in focal segmental glomerulosclerosis lesions.
22310917 - Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy.
18594157 - Severe congenital neutropenia or hyper-igm syndrome? a novel mutation of cd40 ligand in...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiac failure     Volume:  6     ISSN:  1071-9164     ISO Abbreviation:  J. Card. Fail.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-19     Completed Date:  2001-03-22     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9442138     Medline TA:  J Card Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  321-9     Citation Subset:  IM    
Affiliation:
Molecular Cardiology Institute, Highland Park, New Jersey 08904, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Base Sequence / genetics*
Biopsy
Cardiomyopathy, Dilated / classification,  enzymology,  genetics*,  pathology
Case-Control Studies
Child
Child, Preschool
DNA, Mitochondrial / analysis*,  genetics*
DNA, Ribosomal / analysis,  genetics
Humans
Infant
Infant, Newborn
Middle Aged
Mutation, Missense / genetics*
Point Mutation / genetics*
Predictive Value of Tests
Prevalence
RNA, Transfer / analysis*,  genetics*
Sequence Analysis, DNA
Severity of Illness Index
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial; 0/DNA, Ribosomal; 9014-25-9/RNA, Transfer

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Selective upregulation of endothelin converting enzyme-1a in the human failing heart.
Next Document:  Additional use of immunostaining for active caspase 3 and cleaved actin and PARP fragments to detect...