title: Cardiac dysfunction in mitochondrial disease. Clinical and molecular features.
abstract: BACKGROUND
  Mitochondrial disorders (MD) are multisystem diseases that arise as a result of dysfunction of the oxidative phosphorylation system. The predominance of neuromuscular manifestations in MD could mask the presence of other clinical phenotypes such as cardiac dysfunction. Reported here is a retrospective study, the main objective of which was to characterize the clinical and molecular features of a cohort of patients with cardiomyopathy and MD.
  
  
  RESULTS
  Hospital charts of 2,520 patients, evaluated for presumed MD were reviewed. The clinical criterion for inclusion in this study was the presence of a cardiac disturbance accompanied by a mitochondrial dysfunction. Only 71 patients met this criterion. The mitochondrial genome (mtDNA) could be sequenced only in 45 and the pathogenicity of 2 of the found changes was investigated using transmitochondrial cybrids. Three nucleotide changes in mtDNA that may be relevant and 3 with confirmed pathogenicity were identified but no mutations were found in the 13 nuclear genes analyzed.
  
  
  CONCLUSIONS
  The mtDNA should be sequenced in patients with cardiac dysfunction accompanied by symptoms suggestive of MD; databases should be carefully and periodically screened to discard mitochondrial variants that could be associated with MD; functional assays are necessary to classify mitochondrial variants as pathogenic or polymorphic; and additional efforts must be made in order to identify nuclear genes that can explain some as yet uncharacterized molecular features of mitochondrial cardiomyopathy.
authors: Biochemistry Unit, "Hospital Universitario Puerta de Hierro"
authors: Pedro
authors: P
authors: Villar
authors: Begoña
authors: B
authors: Bretón
authors: Pablo
authors: P
authors: García-Pavía
authors: Cristina
authors: C
authors: González-Páramos
authors: Alberto
authors: A
authors: Blázquez
authors: Manuel
authors: M
authors: Gómez-Bueno
authors: Teresa
authors: T
authors: García-Silva
authors: Ines
authors: I
authors: García-Consuegra
authors: Miguel Angel
authors: MA
authors: Martín
authors: Rafael
authors: R
authors: Garesse
authors: Belen
authors: B
authors: Bornstein
authors: M Esther
authors: ME
authors: Gallardo
mesh_terms: D000293:Adolescent; D000328:Adult; D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D054629:Genome, Mitochondrial; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D012189:Retrospective Studies