Development of a high resolution melting method for the detection of genetic variations in hypertrophic cardiomyopathy

Millat, Gilles; Chanavat, Valérie; Crehalet, Hervé; Rousson, Robert

doi:10.1016/j.cca.2010.08.017

Cited by 20 publications

(19 citation statements)

References 35 publications

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“…The findings between the twins are interesting. First, although the single site mutation of MYH7 has been previously reported in HCM, 13) we are the first to report the probable association of MYH7 gene mutation with phenotypic expressivity in monozygotic twins with HCM. Second, the morphologic expression of the twins was similar, but not identical.…”

Section: Discussionmentioning

confidence: 86%

Different Clinical Presentation and Tissue Characterization in a Monozygotic Twin Pair with MYH7 Mutation-Related Hypertrophic Cardiomyopathy

Wang

Han

et al. 2019

Int. Heart J.

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This case report demonstrates a pair of monozygotic twins with hypertrophic cardiomyopathy (HCM) carrying the same pathogenic mutation of MYH7 (p.G768R; c.2302G>A), detected by whole exome and Sanger genetic sequencing methods. On multi-modality imaging, they were reported to have similar, but not identical, morphologic expression. Particularly, the clinical presentation and tissue characteristics were not the same. Late gadolinium enhancement (LGE) and T1 mapping of cardiac magnetic resonance showed different extents of myocardial fibrotic characteristics in the twins (twin A: 16.3% LGE and 32.6% extracellular volume [ECV] of the whole left ventricle; twin B: 5.4% LGE and 28.1% ECV of the whole left ventricle). This extraordinary case of HCM provides evidence on the complex pathophysiological mechanisms of HCM and suggests the likely impact of epigenetics and environmental factors on HCM phenotype.

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Section: Discussionmentioning

confidence: 86%

Different Clinical Presentation and Tissue Characterization in a Monozygotic Twin Pair with MYH7 Mutation-Related Hypertrophic Cardiomyopathy

Wang

Han

et al. 2019

Int. Heart J.

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“…Moreover, HRM population study of exon 14 of TNNT2 gene in 200 chromosomes from healthy control Caucasian Portuguese individuals, allow us to find this allele (rs3730238) in 3 chromosomes from control individuals (1.5%) (Figure 5f and 5g). This SNP has also been found in more European populations, namely in Spanish and French individuals [18,30,31]. Interestingly, it has not been described in more geographically distant populations, such as the Indian population [32].…”

Section: Resultsmentioning

confidence: 97%

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

et al. 2012

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BackgroundHypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine.MethodologyIn this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population.ResultsHRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations.ConclusionsHRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.

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“…In silico testing, including protein predictors and evolutionary conservation, showed that p.Ala1603Thr can be pathogenic. Using high resolution melting (HRM) method, this variant was firstly reported in a cohort of HCM patients [28]. In a recent study, p.Ala1603Thr has also been reported in an HCM patient and it has been deemed as pathogenic in the population study [29].…”

Section: Discussionmentioning

confidence: 97%

Prediction and in silico validation of MYH7 gene missense variants in the Iranian population: a bioinformatics analysis based on Iranome database

Shahbazi

2020

Egypt J Med Hum Genet

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Background: Identifying disease-causing genetic variants in a particular population improves the molecular diagnosis of genetic disorders. National genome databases provide valuable information on this matter. This study aimed to investigate the genomic variants of the MYH7 gene, related to the common heart disease, i.e., hereditary cardiomyopathy. Results: MYH7 gene variants were extracted from the Iranome database and loaded into SPSS software. The filtration steps were performed based on the variant specification and with emphasis on identifying missense changes. Using predictive algorithms, different aspects of the changes such as allele frequency and functional defects were investigated. Our results showed that 41 (17.4%) coding variants were synonymous compared with 18 (7.7%) missense alterations. The missense variants were mostly observed in exons 20-40 that encode MyHC αhelical rod tail. The p.Pro211Leu, p.Arg787His, p.Val964Leu, p.Arg1277Gln, and p.Ala1603Thr were already known to be associated with inherited cardiomyopathy. Four of the missense variants, p.Asn1623Ser, p.Arg1588His, p.Phe1498Tyr, and p.Arg1129Ser, were located on MyHC α-helical rod tail and none of them was annotated on dbSNP or genomAD databases. Conclusion: Our study showed several MYH7 variants associated with the disease in the Iranian population. The results emphasize the importance of analyzing the exons encoding MyHC α-helical rod tail. The investigation of genomic databases can be considered as a cost-effective strategy using targeted mutation detection analyses. The efficacy of this prediction method should be elucidated in further studies on patients' cohorts.

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Development of a high resolution melting method for the detection of genetic variations in hypertrophic cardiomyopathy

Cited by 20 publications

References 35 publications

Different Clinical Presentation and Tissue Characterization in a Monozygotic Twin Pair with MYH7 Mutation-Related Hypertrophic Cardiomyopathy

Different Clinical Presentation and Tissue Characterization in a Monozygotic Twin Pair with MYH7 Mutation-Related Hypertrophic Cardiomyopathy

High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

Prediction and in silico validation of MYH7 gene missense variants in the Iranian population: a bioinformatics analysis based on Iranome database

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