Hypertrophic Cardiomyopathy as an Oligogenic Disease: Transcriptomic Arguments

Baulina, Natalia; Kiselev, Ivan; Чумакова, О. С.; Фаворова, О. О.

doi:10.1134/s0026893320060023

Cited by 11 publications

(6 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the context of cardiovascular disorders, mutations in multiple genes have been implicated in the etiology of conditions such as hypertrophic cardiomyopathy [9] and familial hypercholesterolemia [10]. These disorders exhibit significant genetic heterogeneity, with mutations in different genes contributing to the development and progression of the disease.…”

Section: Examples Of Oligogenic Inheritance In Monogenicmentioning

confidence: 99%

Digenic or oligogenic mutations in presumed monogenic disorders: A review

et al. 2023

View full text Add to dashboard Cite

Monogenic disorders are traditionally attributed to the presence of mutations in a single gene. However, recent advancements in genomics have revealed instances where the phenotypic expression of apparently monogenic disorders cannot be fully explained by mutations in a single gene alone. This review article aims to explore the emerging concept of digenic or oligogenic inheritance in seemingly monogenic disorders. We discuss the underlying mechanisms, clinical implications, and the challenges associated with deciphering the contribution of multiple genes in the development and manifestation of such disorders. We present relevant studies and highlight the importance of adopting a broader genetic approach in understanding the complex genetic architecture of these conditions.

show abstract

Section: Examples Of Oligogenic Inheritance In Monogenicmentioning

confidence: 99%

Digenic or oligogenic mutations in presumed monogenic disorders: A review

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Genetic modifiers usually include DNA methylation and acetylation, and the importance of miRNA has recently been discussed [ 24 ]. It is possible that newly discovered variants of non-sarcomeric genes, e.g., for ion channels, desmosomes, or titin, are not the primary cause of HCM, but the mentioned modifiers [ 12 , 17 , 71 , 72 , 73 ].…”

Section: Genotype and Phenotype Correlationmentioning

confidence: 99%

Genetic Testing in Patients with Hypertrophic Cardiomyopathy

Bonaventura

Poláková

Vejtasová

et al. 2021

IJMS

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is considered a Mendelian disease, with mainly autosomal dominant inheritance. Most pathogenic variants are usually detected in genes for sarcomeric proteins. Nowadays, the genetic basis of HCM is believed to be rather complex. Thousands of mutations in more than 60 genes have been described in association with HCM. Nevertheless, screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the interpretation of the results difficult. Patients lacking a pathogenic variant are now believed to have non-Mendelian HCM and probably have a better prognosis than patients with sarcomeric pathogenic mutations. Identifying the genetic basis of HCM creates remarkable opportunities to understand how the disease develops, and by extension, how to disrupt the disease progression in the future. The aim of this review is to discuss the brief history and recent advances in the genetics of HCM and the application of molecular genetic testing into common clinical practice.

show abstract

“…The main concern in studying HCM is its extremely high genetic, morphological and clinical heterogeneity. Approximately 60% of HCM-phenotype presenting patients have pathogenic/likely pathogenic (P/LP) variants in sarcomere or sarcomere-associated genes [ 3 ]. About 80% of the P/LP variants in these genes are detected in MYH7 and MYBPC3 , which encode β-myosin heavy chain and myosin-binding protein C, respectively [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-499a-5p Is a Potential Biomarker of MYH7—Associated Hypertrophic Cardiomyopathy

Baulina

Pisklova

Kiselev

et al. 2022

IJMS

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disease with significant genetic and phenotypic heterogeneity. To search for novel biomarkers, which could increase the accuracy of HCM diagnosis and improve understanding of its phenotype formation, we analyzed the levels of circulating miRNAs—stable non-coding RNAs involved in post-transcriptional gene regulation. Performed high throughput sequencing of miRNAs in plasma of HCM patients and controls pinpointed miR-499a-5p as one of 35 miRNAs dysregulated in HCM. Further investigation on enlarged groups of individuals showed that its level was higher in carriers of pathogenic/likely pathogenic (P/LP) variants in MYH7 gene compared to controls (fold change, FC = 8.9; p < 0.0001). Just as important, carriers of variants in MYH7 gene were defined with higher miRNA levels than carriers of variants in the MYBPC3 gene (FC = 14.1; p = 0.0003) and other patients (FC = 4.1; p = 0.0008). The receiver operating characteristic analysis analysis showed the ability of miR-499a-5p to identify MYH7 variant carriers with the HCM phenotype with area under the curve value of 0.95 (95% confidence interval: 0.88–1.03, p = 0.0004); sensitivity and specificity were 0.86 and 0.91 (cut-off = 0.0014). Therefore, miR-499a-5p could serve as a circulating biomarker of HCM, caused by P/LP variants in MYH7 gene.

show abstract

Hypertrophic Cardiomyopathy as an Oligogenic Disease: Transcriptomic Arguments

Cited by 11 publications

References 69 publications

Digenic or oligogenic mutations in presumed monogenic disorders: A review

Digenic or oligogenic mutations in presumed monogenic disorders: A review

Genetic Testing in Patients with Hypertrophic Cardiomyopathy

Circulating miR-499a-5p Is a Potential Biomarker of MYH7—Associated Hypertrophic Cardiomyopathy

Contact Info

Product

Resources

About