Maternally inherited cardiomyopathy: clinical and molecular characterization of a large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid
| Autor: | Domenico A. Coviello, Carlo Casali, Filippo M. Santorelli, Giulia d'Amati, Pietro Gallo, Luciano Debiase, Camillo Autore, Paola Bernucci |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Mitochondrial DNA X Chromosome Heart disease Adolescent Genetic counseling DNA Mutational Analysis Cardiomyopathy DNA Mitochondrial Genetic determinism Pregnancy Medicine Humans Point Mutation Genetic Predisposition to Disease Child RNA Transfer Ile Sex Chromosome Aberrations Aged Genetics Aged 80 and over Heart Failure business.industry Point mutation Hypertrophic cardiomyopathy Cardiomyopathy Hypertrophic Middle Aged medicine.disease Pedigree Phenotype Heart failure Child Preschool Female business Cardiology and Cardiovascular Medicine Polymorphism Restriction Fragment Length |
| Zdroj: | Journal of the American College of Cardiology. 33(6) |
| ISSN: | 0735-1097 |
| Popis: | OBJECTIVES 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. |
| Databáze: | OpenAIRE |
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