A rare case of familial restrictive cardiomyopathy with mutations in MYH7 and ABCC9 genes

Neagoe, Oana; Ciobanu, Anda; Diaconu, Rodica; Mirea, Oana; Donoiu, Ionuţ; Militaru, Constantin

doi:10.15190/d.2019.12

Cited by 8 publications

(5 citation statements)

References 20 publications

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“…The SCDY/DCM associated p.R1186Q variant resides within TMD2. This variant was previously detected in a heterozygous state in a human with restrictive cardiomyopathy; however, the presence of a concurrent variant in MYH7, an established susceptibility gene for restrictive cardiomyopathy, complicated prediction of the role of the ABCC9 variant in the cardiac phenotype of that patient [48,55]. A nearby rare variant in the TMD2, p.R1197C (rs778849288), has been identified in humans with sudden unexplained nocturnal death syndrome or DCM [7,47].…”

Section: Discussionmentioning

confidence: 99%

“…ABCC9 p.R1186Q is a rare variant in humans (rs776973456, allele frequency ≤ 0.0007), detected in American, European, and Korean populations. It has been previously reported in a heterozygous state in a human with restrictive cardiomyopathy that also had a heterozygous variant in MHY7 (encoding β-myosin heavy chain) [48]. Another missense variant, p.R1186W (rs886049169), also exists at this residue in humans at lower frequency (allele frequency ≤ 0.000007).…”

Section: Homologous Abcc9 Variants In Human Databasesmentioning

confidence: 94%

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An ABCC9 Missense Variant Is Associated with Sudden Cardiac Death and Dilated Cardiomyopathy in Juvenile Dogs

Furrow

Tate

Minor

et al. 2023

Genes

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Sudden cardiac death in the young (SCDY) is a devastating event that often has an underlying genetic basis. Manchester Terrier dogs offer a naturally occurring model of SCDY, with sudden death of puppies as the manifestation of an inherited dilated cardiomyopathy (DCM). We performed a genome-wide association study for SCDY/DCM in Manchester Terrier dogs and identified a susceptibility locus harboring the cardiac ATP-sensitive potassium channel gene ABCC9. Sanger sequencing revealed an ABCC9 p.R1186Q variant present in a homozygous state in all SCDY/DCM-affected dogs (n = 26). None of the controls genotyped (n = 398) were homozygous for the variant, but 69 were heterozygous carriers, consistent with autosomal recessive inheritance with complete penetrance (p = 4 × 10−42 for the association of homozygosity for ABCC9 p.R1186Q with SCDY/DCM). This variant exists at low frequency in human populations (rs776973456) with clinical significance previously deemed uncertain. The results of this study further the evidence that ABCC9 is a susceptibility gene for SCDY/DCM and highlight the potential application of dog models to predict the clinical significance of human variants.

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Section: Discussionmentioning

confidence: 99%

Section: Homologous Abcc9 Variants In Human Databasesmentioning

confidence: 94%

An ABCC9 Missense Variant Is Associated with Sudden Cardiac Death and Dilated Cardiomyopathy in Juvenile Dogs

Furrow

Tate

Minor

et al. 2023

Genes

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“…Routine echocardiographic examinations were performed at the echocardiography core facility [ 12 , 13 ]. The patients were examined in the left lateral decubitus position by using the dedicated ultrasound equipment (GE-Vivid S6, Avante Health Solution, Concord, NC, USA) with a 3.5 MHz transducer.…”

Section: Methodsmentioning

confidence: 99%

Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study

Diaconu

Schaaps

Afify

et al. 2021

IJMS

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ApoE abnormality represents a well-known risk factor for cardiovascular diseases. Beyond its role in lipid metabolism, novel studies demonstrate a complex involvement of apoE in membrane homeostasis and signaling as well as in nuclear transcription. Due to the large spread of apoE isoforms in the human population, there is a need to understand the apoE’s role in pathological processes. Our study aims to dissect the involvement of apoE in heart failure. We showed that apoE-deficient rats present multiple organ damages (kidney, liver, lung and spleen) besides the known predisposition for obesity and affected lipid metabolism (two-fold increase in tissular damages in liver and one-fold increase in kidney, lung and spleen). Heart tissue also showed significant morphological changes in apoE−/− rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE−/− rats fed a high-fat diet showed more damage and affected collagen content (~60% less total collagen content and double increase in collagen1/collagen3 ratio) compared with the left ventricle (no significant differences in total collagen content or collagen1/collagen3 ratio). In patients, we were able to find a correlation between the presence of ε4 allele and cardiomyopathy (χ2 = 10.244; p = 0.001), but also with right ventricle dysfunction with decreased TAPSE (15.3 ± 2.63 mm in ε4-allele-presenting patients vs. 19.8 ± 3.58 mm if the ε4 allele is absent, p < 0.0001*) and increased in systolic pulmonary artery pressure (50.44 ± 16.47 mmHg in ε4-allele-presenting patients vs. 40.68 ± 15.94 mmHg if the ε4 allele is absent, p = 0.0019). Our results confirm that the presence of the ε4 allele is a lipid-metabolism-independent risk factor for heart failure. Moreover, we show for the first time that the presence of the ε4 allele is associated with right ventricle dysfunction, implying different regulatory mechanisms of fibroblasts and the extracellular matrix in both ventricles. This is essential to be considered and thoroughly investigated before the design of therapeutical strategies for patients with heart failure.

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“…21 The most common genetic defect seen in FRCM is in the gene TNNI3, which encodes for cardiac troponin I; however, MYH7, TNNT2, TPM1, MYL2/3, and ACTC1 have also been known to lead to this condition. 22 The frequency of ACM in the general population is between 1:1000 and 1:5000. 23 ACM was previously thought to be a disease localized to northeastern Italy.…”

Section: Classification Epidemiology and Pathophysiology Of Cardiomyo...mentioning

confidence: 99%

Section: Classification Epidemiology and Pathophysiology Of Cardiomyo...mentioning

confidence: 99%

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives

Huang,

Verma,

Mok

et al. 2024

Glob Med Genet

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Background Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.

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A rare case of familial restrictive cardiomyopathy with mutations in MYH7 and ABCC9 genes

Cited by 8 publications

References 20 publications

An ABCC9 Missense Variant Is Associated with Sudden Cardiac Death and Dilated Cardiomyopathy in Juvenile Dogs

An ABCC9 Missense Variant Is Associated with Sudden Cardiac Death and Dilated Cardiomyopathy in Juvenile Dogs

Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives

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