Iris Schrijver

Publication Details

  • Mitochondrial DNA analysis by multiplex denaturing high-performance liquid chromatography and selective sequencing in pediatric patients with cardiomyopathy GENETICS IN MEDICINE Schrijver, I., Pique, L. M., Traynis, I., Scharfe, C., Sehnert, A. J. 2009; 11 (2): 118-126

    Abstract:

    Mitochondrial DNA testing is typically performed by targeted mutation analysis only. We applied a more comprehensive approach to study the mitochondrial genome in 24 pediatric patients with idiopathic cardiomyopathy.Patients in the cohort did not show overt multisystemic disease and were previously tested for mutations in a subset of structural genes associated with cardiomyopathy. Mutation screening of the mitochondrial DNA by multiplex denaturing high-performance liquid chromatography was complemented by sequence analysis.We identified 130 individual (unique) sequence changes. Among several potentially pathogenic changes, a novel heteroplasmic mutation in nicotinamide adenine dinucleotide dehydrogenase subunit 4 (10677G>A) was identified in one fraternal twin with worse clinical symptoms than his sibling. Another proband carried homoplasmic mutation 13708G>A (in nicotinamide adenine dinucleotide dehydrogenase subunit 5) that has been associated with Leber's hereditary optic neuropathy.Changes in mitochondrial DNA may represent a relatively rare cause of idiopathic pediatric cardiomyopathies and/or influence their phenotypic expression. Interpretation of variants with uncertain pathogenicity, however, currently impedes clinical diagnostic use of comprehensive mitochondrial DNA testing. Whereas combined use of multiplex denaturing high-performance liquid chromatography and sequencing is more comprehensive than targeted mutation analysis, measurement of additional functional parameters, such as tissue respiratory chain activity, remains important to establishing a definitive diagnosis.

    View details for DOI 10.1097/GIM.0b013e318190356b

    View details for Web of Science ID 000263663300009

    View details for PubMedID 19265752

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