title: Maternally inherited cardiomyopathy: clinical and molecular characterization of a large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid.
abstract: OBJECTIVE
  The purpose of this study was to describe the clinical and molecular features of a large family with maternally inherited cardiomyopathy (MICM).
  
  
  BACKGROUND
  Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information.
  
  
  METHODS
  Clinical and genetic analysis of the family was carried out.
  
  
  RESULTS
  Echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. Neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDNA genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood.
  
  
  CONCLUSIONS
  This report contributes a better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDNA mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial DNA defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients.
authors.affiliation: Istituto di Clinica delle Malattie Nervose e Mentali, Università di Roma-La Sapienza, Rome, Italy. Casali@uniroma1.it
authors.forename: C
authors.initials: C
authors.lastname: Casali
authors.forename: G
authors.initials: G
authors.lastname: d'Amati
authors.forename: P
authors.initials: P
authors.lastname: Bernucci
authors.forename: L
authors.initials: L
authors.lastname: DeBiase
authors.forename: C
authors.initials: C
authors.lastname: Autore
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: D
authors.initials: D
authors.lastname: Coviello
authors.forename: P
authors.initials: P
authors.lastname: Gallo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D012355:RNA, Transfer, Ile / Q000235:genetics; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D014960:X Chromosome
chemical_list: D004272:DNA, Mitochondrial; D012355:RNA, Transfer, Ile