Familial cardiomyopathies associated to mitochondrial dna mutations: report of two families

C. Casali, F. M. Santorelli, C. Bruno, D. Fortini, M. Damiano, G. D'Amati, M. Spadaro

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Familial cardiomyopathies are clinically and genetically heterogeneous diseases in which inherited alterations of sarcomeric proteins account for about 50% of affected families. Since heart is heavily dependent upon oxidative phosphorylation (OXPHOS), one would expect that mitochondrial DNA (mtDNA) alterations, affect cardiac function. We have carried out prospective and retrospective mtDNA analyses in families in whom cardiac symptoms represented the predominant, if not sole, clinical manifestation.Case 1. A 6-month-old infant presented with hypotonia and progressive respiratory distress. Ecocardiography showed severe hypertrophie cardiomyopathy. Histochemistry showed lipid droplets and several cytochrome c oxidase negative fibers in skeletal muscle biopsy. Biochemistry revealed decreased OXPHOS activities in muscle and mitochondrial proliferation in heart. A 2-year-old sister had longstanding asthma and a maternal cousin suffered a heart attack in his 20's. We identified the C3303T mutation in the tRNALeu(UUR) gene in very high proportions (>98%) in heart and muscle mitochondrial genomes from the propositus This mutation has been associated in one family with severe infantile hypertrophie cardiomyopathy. Case 2. A 7-year-old boy suddenly collapsed while playing, because of cardiorespiratory arrest. Past medical history was significant for developmental delay and an episode of congestive heart failure at age 6 months. Muscle biopsy showed increased lipid droplets and subsarcotemmal mitochondrial aggregates. Biochemistry showed reduced complexes I and IV of the respiratory chain in muscle. Family history was remarkable for two similarly affected siblings. We identified a novel mtDNA mutation (T12297C) in the tRNALeu(CUN) gene which alters an evolutionarily conserved nucleotide thus meeting the current criteria for pathogenicity. MtDNA alterations should be considered in familial cardiomyopathies with altered OXPHOS, especially when maternal transmission is evident.

Original languageEnglish
Pages (from-to)61
Number of pages1
JournalItalian Journal of Neurological Sciences
Issue number4
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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