NGS data validated by Sanger sequencing reveal a puzzling small deletion of  MYBPC3 gene associated with hypertrophic cardiomyopathy

Micheu, Miruna Mihaela; Popa-Fotea, Nicoleta-Monica; Oprescu, Nicoleta; Dorobanțu, Maria; Rațiu, Attila Cristian; Ecovoiu, Alexandru Al.

doi:10.25083/rbl/24.1/91.99

Cited by 10 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients in the HCM group underwent genetic testing following a methodology that was described in detail elsewhere [ 14 , 15 ]. In summary, blood samples were collected at enrollment, and DNA was isolated using the MagCore Genomic DNA Whole Blood Kit (RBC Bioscience, Taipei, Taiwan).…”

Section: Methodsmentioning

confidence: 99%

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy

et al. 2021

Self Cite

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) and arterial hypertension (HTN) are conditions with different pathophysiology, but both can result in left-ventricular hypertrophy (LVH). The role of left-atrial (LA) functional changes detected by two-dimensional speckle-tracking echocardiography (STE) in indicating LVH etiology is unknown. Methods: We aimed to characterize LA mechanics using STE in LVH patients with HCM and HTN. LA 2D volumetric and STE parameters were analyzed in 86 LVH patients (43 HCM and 43 isolated HTN subjects) and 33 age- and sex-matched controls. Results: The volumetric study showed that LA reservoir and conduit function were impaired in the HCM group compared to controls, while, in the HTN group, only LA conduit function was deteriorated. The HCM group had all three STE-derived LA functions impaired compared to controls. The HTN group, consistently with volumetric analysis, had solely LA conduit function reduced compared to controls. Ratios of LA booster-pump strain (S) and strain rate (SR) to interventricular septum (IVS) thickness were the most accurate parameters to discriminate between HCM and HTN. The subgroup harboring sarcomeric pathogenic (P)/likely pathogenic (LP) variants had reduced LA booster-pump S and SR compared with the genotype-negative subgroup. Conclusions: LA reservoir, conduit, and pump functions are decreased in HCM compared to HTN patients with similar LVH. We report the ratios between LA contraction S/SR and IVS thickness as novel parameters with high accuracy in discriminating LVH due to HCM. The presence of P/LP variants in sarcomeric or sarcomeric-associated genes could be associated with more severe LA dysfunction.

show abstract

Section: Methodsmentioning

confidence: 99%

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The use of high-throughput sequencing techniques and wide-ranging cardiac gene panels dramatically increased the detection of variants of uncertain significance (VUS) [ 183 , 184 , 185 , 186 ], whose definite classification requires additional studies including functional ones. The previously presented data, as well as data from Table 2 , demonstrate the structural and functional homologies between fruit fly and human cardiac genes and advocate the use of D. melanogaster system as a prime candidate to study and validate genetic variants associated with cardiac disorders.…”

Section: Cardiac Disordersmentioning

confidence: 99%

Inter-Species Rescue of Mutant Phenotype—The Standard for Genetic Analysis of Human Genetic Disorders in Drosophila melanogaster Model

Ecovoiu

Rațiu

Micheu

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Drosophila melanogaster (the fruit fly) is arguably a superstar of genetics, an astonishing versatile experimental model which fueled no less than six Nobel prizes in medicine. Nowadays, an evolving research endeavor is to simulate and investigate human genetic diseases in the powerful D. melanogaster platform. Such a translational experimental strategy is expected to allow scientists not only to understand the molecular mechanisms of the respective disorders but also to alleviate or even cure them. In this regard, functional gene orthology should be initially confirmed in vivo by transferring human or vertebrate orthologous transgenes in specific mutant backgrounds of D. melanogaster. If such a transgene rescues, at least partially, the mutant phenotype, then it qualifies as a strong candidate for modeling the respective genetic disorder in the fruit fly. Herein, we review various examples of inter-species rescue of relevant mutant phenotypes of the fruit fly and discuss how these results recommend several human genes as candidates to study and validate genetic variants associated with human diseases. We also consider that a wider implementation of this evolutionist exploratory approach as a standard for the medicine of genetic disorders would allow this particular field of human health to advance at a faster pace.

show abstract

“…Sequencing of wide-ranging gene panels by high-throughput techniques on a daily basis has increased the rate of positive genetic testing, and it has also increased the detection of variants of uncertain significance (VUS). Recently, our group reported the yield of DNA testing in a cohort of HCM probands[ 134 , 135 ]. Nearly half (45%) of the rare variants identified in our study were novel, and thus classified as of VUS.…”

Section: Modeling Variants Of Uncertain Significancementioning

confidence: 99%

Patient-specific induced pluripotent stem cells as “disease-in-a-dish” models for inherited cardiomyopathies and channelopathies – 15 years of research

Micheu¹,

Rosca²

2021

WJSC

Self Cite

View full text Add to dashboard Cite

Among inherited cardiac conditions, a special place is kept by cardiomyopathies (CMPs) and channelopathies (CNPs), which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality. Like other inherited cardiac conditions, genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant, challenging our understanding of the underlying pathogenic mechanisms. Until recently, the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms. The advent of induced pluripotent stem cell (iPSC) technology, along with advances in gene editing, offered unprecedented opportunities to explore hereditary CMPs and CNPs. Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers, genetic identity with the subject from whom they were derived, and ease of gene editing, all of which were used to generate “disease-in-a-dish” models of monogenic cardiac conditions. Functionally, iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype, allowed the study of disease mechanisms in an individual-/allele-specific manner, as well as the customization of therapeutic regimen. This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms, personalized therapy and deoxyribonucleic acid variant functional annotation.

show abstract

NGS data validated by Sanger sequencing reveal a puzzling small deletion of MYBPC3 gene associated with hypertrophic cardiomyopathy

Cited by 10 publications

References 14 publications

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy

Inter-Species Rescue of Mutant Phenotype—The Standard for Genetic Analysis of Human Genetic Disorders in Drosophila melanogaster Model

Patient-specific induced pluripotent stem cells as “disease-in-a-dish” models for inherited cardiomyopathies and channelopathies – 15 years of research

Contact Info

Product

Resources

About