Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes

Ware, Stephanie M.; ElHassan, Nahed O.; Kahler, Stephen G.; Zhang, Q.; Mai, Y. W.; Miller, Erin; Wong, Brenda; Spicer, Robert L.; Craigen, William J.; Kozel, Beth A.; Grange, Dorothy K.; Wong, Lee‐Jun

doi:10.1136/jmg.2008.063149

Cited by 86 publications

(54 citation statements)

References 24 publications

(23 reference statements)

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“…The entire mitochondrial genome was amplified by using 24 pairs of sequence-specific overlapping primers (17)(18)(19). GenBank sequence NC_012920.1 was used as a reference.…”

Section: Selection Of Dna Samples For Mps Analysismentioning

confidence: 99%

Comprehensive One-Step Molecular Analyses of Mitochondrial Genome by Massively Parallel Sequencing

2012

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BACKGROUND:Mitochondrial diseases are clinically and genetically heterogeneous, with variable penetrance, expressivity, and differing age of onset. Diseasecausing point mutations and large deletions in the mitochondrial genome often exist in a heteroplasmic state. Current molecular analyses require multiple different and complementary methods for the detection and quantification of mitochondrial DNA (mtDNA) mutations. We developed a novel approach to analyze the mtDNA in 1 step.

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“…The entire mitochondrial genome was amplified by using 24 pairs of sequence-specific overlapping primers (17)(18)(19). GenBank sequence NC_012920.1 was used as a reference.…”

Section: Selection Of Dna Samples For Mps Analysismentioning

confidence: 99%

Comprehensive One-Step Molecular Analyses of Mitochondrial Genome by Massively Parallel Sequencing

2012

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“…[10][11][12] Purified PCR products were sequenced using BigDye Terminator (Life Technologies, Green Island, NY) chemistry on an ABI3730XL automated DNA sequencer (Life Technologies).…”

Section: Sanger Sequencingmentioning

confidence: 99%

Comprehensive next-generation sequence analyses of the entire mitochondrial genome reveal new insights into the molecular diagnosis of mitochondrial DNA disorders

Cui

Chen

et al. 2013

Genetics in Medicine

111

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1-3Pathogenic mtDNA mutations, ranging from point mutations to large deletions, are often present in mixed proportions with wildtype mtDNA molecules within the same cell, a biological phenomenon termed heteroplasmy. The degree of mtDNA mutant heteroplasmy can vary significantly across different tissues of the same individual, and the percentage of a mutation is an important contributor to the clinical phenotype.4,5 Determination of the heteroplasmic status of any mtDNA mutation is clinically important to providing a family with informative genetic counseling regarding recurrence risk. Therefore, accurate measurement of heteroplasmy is an essential component of the molecular diagnostic scheme for mtDNA-related disorders.The diagnosis of an individual with suspected mtDNA-related disorders begins with a thorough clinical evaluation and assessment of family history.6 If a disorder with matrilineal inheritance can be established, common mtDNA point mutations and large deletions are typically analyzed using PCR-based targeted assays and Southern blotting methodology. If the screening for common point mutations and large deletions is negative, then the entire mitochondrial genome is usually analyzed by a conventional PCR-based Sanger sequencing approach with multiple pairs of primers. When a mutation is identified, analysis of the degree of heteroplasmy is carried out using various methods, including the commonly used allele refractory mutation system-based quantitative PCR (ARMS qPCR) for quantitative measurement.7 Large deletions are usually confirmed by PCR using primers encompassing the deletion break points followed by sequence analysis to map the break points, or, alternatively, by oligonucleotide array comparative genome hybridization.8 These sequential approaches are time consuming and costly. In an effort to improve efficiency and sensitivity of mtDNA mutation detection, we recently developed a comprehensive one-step long range/massively parallel sequencing (LR-PCR/MPS)-based approach that uses a single pair of PCR primers to amplify the entire mitochondrial genome. This method allows the simultaneous detection of point mutations with quantified heteroplasmy as well as large mtDNA deletions with accurately mapped break points. Purpose: The application of massively parallel sequencing technology to the analysis of the mitochondrial genome has demonstrated great improvement in the molecular diagnosis of mitochondrial DNA-related disorders. The objective of this study was to investigate the performance characteristics and to gain new insights into the analysis of the mitochondrial genome. Methods:The entire mitochondrial genome was analyzed as a single amplicon using a long-range PCR-based enrichment approach coupled with massively parallel sequencing. The interference of the nuclear mitochondrial DNA homologs was distinguished from the actual mitochondrial DNA sequences by comparison with the results obtained from conventional PCR-based Sanger sequencing using multiple pairs of primers. Results:Our results demo...

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“…One child had a tentative diagnosis of coexistent Wolff-Parkinson-White. 93 HCM phenotypes also are reported for MTTG.…”

Section: Mitochondrial Diseasementioning

confidence: 91%

Genetic Cardiomyopathies Causing Heart Failure

Cahill

Ashrafian

Watkins

2013

Circulation Research

144

117

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Despite the striking advances in medical and surgical therapy, the morbidity, mortality, and economic burden of heart failure (HF) remain unacceptably high. There is increasing evidence that the risk and course of HF depend on genetic predisposition; however, the genetic contribution to HF is heterogeneous and complex. At one end of the spectrum are the familial monogenic HF syndromes in which causative mutations are rare but highly penetrant. At the other, HF susceptibility and course may be influenced by more common, less penetrant genetic variants. As detailed in this review, efforts to unravel the basis of the familial cardiomyopathies at the mendelian end of the spectrum already have begun to deliver on the promise of informative mechanisms, novel gene-based diagnostics, and therapies for distinct subtypes of HF. However, continued progress requires the differentiation of pathogenic mutations, disease modifiers, and rare, benign variants in the deluge of data emerging from increasingly accessible novel sequencing technologies. This represents a significant challenge and demands a sustained effort in analysis of extended family pedigrees, diligent clinical phenotyping, and systematic annotation of human genetic variation. (Circ Res. 2013;113:660-675.)

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Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes

Abstract: Mitochondrial genome sequencing should be considered in patients with infantile hypertrophic cardiomyopathy.

Cited by 86 publications

References 24 publications

Comprehensive One-Step Molecular Analyses of Mitochondrial Genome by Massively Parallel Sequencing

Comprehensive One-Step Molecular Analyses of Mitochondrial Genome by Massively Parallel Sequencing

Comprehensive next-generation sequence analyses of the entire mitochondrial genome reveal new insights into the molecular diagnosis of mitochondrial DNA disorders

Genetic Cardiomyopathies Causing Heart Failure

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