Clinical utility gene card for: Dilated Cardiomyopathy (CMD)

Pósafalvi, Anna; Herkert, Johanna C.; Sinke, Richard J.; Berg, Maarten P. van den; Mogensen, Jens; Jongbloed, Jan D. H.; Tintelen, J. Peter van

doi:10.1038/ejhg.2012.276

Cited by 33 publications

(28 citation statements)

References 23 publications

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“…Hereditary cardiomyopathies are highly heterogeneous disorders, and include dilated (DCM), hypertrophic (HCM), and arrhythmogenic right ventricular cardiomyopathies (ARVC), which are leading causes of heart failure and sudden death. Approximately 30%–50% of DCM cases are familial, but with significant genetic and phenotypic heterogeneity [Posafalvi et al., ]. Particularly for DCM, for which more than 50 cardiomyopathy‐related genes have been identified, targeted resequencing would be a much better diagnostic platform than SS.…”

Section: Introductionmentioning

confidence: 99%

Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics

et al. 2013

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Mutation detection through exome sequencing allows simultaneous analysis of all coding sequences of genes. However, it cannot yet replace Sanger sequencing (SS) in diagnostics because of incomplete representation and coverage of exons leading to missing clinically relevant mutations. Targeted next-generation sequencing (NGS), in which a selected fraction of genes is sequenced, may circumvent these shortcomings. We aimed to determine whether the sensitivity and specificity of targeted NGS is equal to those of SS. We constructed a targeted enrichment kit that includes 48 genes associated with hereditary cardiomyopathies. In total, 84 individuals with cardiomyopathies were sequenced using 151 bp paired-end reads on an Illumina MiSeq sequencer. The reproducibility was tested by repeating the entire procedure for five patients. The coverage of ≥30 reads per nucleotide, our major quality criterion, was 99% and in total ∼21,000 variants were identified. Confirmation with SS was performed for 168 variants (155 substitutions, 13 indels). All were confirmed, including a deletion of 18 bp and an insertion of 6 bp. The reproducibility was nearly 100%. We demonstrate that targeted NGS of a disease-specific subset of genes is equal to the quality of SS and it can therefore be reliably implemented as a stand-alone diagnostic test.

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Section: Introductionmentioning

confidence: 99%

Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics

et al. 2013

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“…51 To date, mutations in 51 genes have been reported to cause DCM. 52 Diverse inheritance patterns and a large number of causative genes make molecular diagnostics of DCM a challenge.…”

Section: An Exemplar In Cardiogenomics: Genetics Of Dilated Cardiomyomentioning

confidence: 99%

Short Read (Next-Generation) Sequencing

Punetha

Hoffman

2013

Circ Cardiovasc Genet

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“…Familial DCM is usually inherited as autosomal dominant, although, autosomal recessive, X‐linked, or mitochondrial inheritance patterns are observed in a small number of cases reflecting a wide locus heterogeneity for its etiology. Currently, more than 50 genes, which encode cytoskeletal, mitochondrial, nucleoskeletal, and calcium‐handling proteins, have been documented to cause DCM . Reduced penetrance and phenotypic variability phenomena have also been reported in DCM .…”

Section: Introductionmentioning

confidence: 99%

“…Currently, more than 50 genes, which encode cytoskeletal, mitochondrial, nucleoskeletal, and calcium‐handling proteins, have been documented to cause DCM . Reduced penetrance and phenotypic variability phenomena have also been reported in DCM . Locus heterogeneity and allelic disorders may also complicate this scenario; that is, the type of gene and mutation often leads to difference in the clinical features, age of onset, and prognosis of DCM.…”

Section: Introductionmentioning

confidence: 99%

Genotypic effect of a mutation of the MYBPC3 gene and two phenotypes with different patterns of inheritance

Mahdieh

Moghaddam

Motavaf

et al. 2018

Clinical Laboratory Analysis

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Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients.

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Clinical utility gene card for: Dilated Cardiomyopathy (CMD)

Cited by 33 publications

References 23 publications

Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics

Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics

Short Read (Next-Generation) Sequencing

Genotypic effect of a mutation of the MYBPC3 gene and two phenotypes with different patterns of inheritance

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