The mitochondrial DNA C3303T mutation can cause cardiomyopathy and/or skeletal myopathy
1The H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia Presbyterian Medical Center, New York, New York, USA.
Insights
The C3303T mitochondrial DNA mutation is confirmed as pathogenic and may cause infantile cardiomyopathy and skeletal myopathies. This genetic mutation should be considered in infant diagnoses.
Area of Science:
- Genetics
- Mitochondrial Diseases
- Cardiology
Background:
- Mitochondrial DNA mutations are linked to infantile cardiomyopathy.
- The C3303T mutation in tRNA(Leu(UUR)) is a suspected cause, but requires further family studies.
- Establishing the mutation's frequency and clinical spectrum is crucial.
Purpose of the Study:
- Determine the frequency of the C3303T mutation in families with maternal inheritance and cardiomyopathy.
- Define the clinical presentation associated with the C3303T mutation.
- Confirm the pathogenicity of the C3303T mutation.
Main Methods:
- Studied families with cardiomyopathy and maternal inheritance.
- Utilized polymerase chain reaction/restriction fragment length polymorphism analysis.
- Screened for the C3303T mutation in mitochondrial DNA.
Main Results:
- Identified the C3303T mutation in 8 patients across 4 unrelated families.
- Observed varied clinical presentations including infantile cardiomyopathy, limb/neck weakness, isolated skeletal myopathy, and combined myopathy/cardiomyopathy.
- Documented fatal infantile cardiomyopathy in one case.
Conclusions:
- Confirmed the pathogenicity of the C3303T mutation.
- Suggests the C3303T mutation is not rare.
- Recommends considering C3303T in differential diagnoses for skeletal myopathies and cardiomyopathy, particularly in infants.
Objective:
Several mutations in mitochondrial DNA have been associated with infantile cardiomyopathy, including a C3303T mutation in the mitochondrial transfer RNA(Leu(UUR)) gene. Although this mutation satisfied generally accepted criteria for pathogenicity, its causative role remained to be confirmed in more families. Our objective was to establish the frequency of the C3303T mutation and to define its clinical presentation.
Study Design:
Families with cardiomyopathy and maternal inheritance were studied by polymerase chain reaction/restriction fragment length polymorphism analysis looking for the C3303T mutation.
Results:
We found the C3303T mutation in 8 patients from 4 unrelated families. In one, the clinical presentation was infantile cardiomyopathy; in the second family, proximal limb and neck weakness dominated the clinical picture for the first 10 years of life, when cardiac dysfunction became apparent; in the third family, 2 individuals presented with isolated skeletal myopathy and 2 others with skeletal myopathy and cardiomyopathy; in the fourth family, one patient had fatal infantile cardiomyopathy and the other had a combination of skeletal myopathy and cardiomyopathy.
Conclusions:
Our findings confirm the pathogenicity of the C3303T mutation and suggest that this mutation may not be rare. The C3303T mutation should be considered in the differential diagnosis of skeletal myopathies and cardiomyopathy, especially when onset is in infancy.
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