Genetic Insights into Primary Restrictive Cardiomyopathy

Brodehl, Andreas; Gerull, Brenda

doi:10.3390/jcm11082094

Cited by 26 publications

(16 citation statements)

References 232 publications

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“…However, there are few common characteristics of the disease: the clinical suspect requires invasive cardiac catheterization for diagnosis; in Western countries, a considerable proportion of paediatric patients with RCM present sarcomeric or non-sarcomeric gene variants. A family history of cardiomyopathy is common, underlining the importance of genetic counselling [113].…”

Section: Discussionmentioning

confidence: 99%

Focus on Paediatric Restrictive Cardiomyopathy: Frequently Asked Questions

Zampieri,

Di Filippo,

Zocchi

et al. 2023

Diagnostics

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Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular pathophysiology determined by increased myocardial stiffness. While suspicion of RCM is initially raised by clinical evaluation and supported by electrocardiographic and echocardiographic findings, invasive hemodynamic evaluation is often required for diagnosis and management of patients during follow-up. RCM is commonly associated with a poor prognosis and a high incidence of heart failure, and PH is reported in paediatric patients with RCM. Currently, only a few therapies are available for specific RCM aetiologies. Early referral to centres for advanced heart failure treatment is often necessary. The aim of this review is to address questions frequently asked when facing paediatric patients with RCM, including issues related to aetiologies, clinical presentation, diagnostic process and prognosis.

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Section: Discussionmentioning

confidence: 99%

Focus on Paediatric Restrictive Cardiomyopathy: Frequently Asked Questions

Zampieri,

Di Filippo,

Zocchi

et al. 2023

Diagnostics

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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%

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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“…In arrhythmogenic cardiomyopathy (ACM), most pathogenic variants are in genes encoding desmosomal proteins such as Plakoglobin ( JUP ) ( 13 , 41 ), DSP ( 48 ), Plakophilin-2 ( PKP2 ), Desmoglein-2 ( DSG2 ) and Desmocollin-2 ( DSC2 ) ( 4 , 51 , 67 ). Finally, inherited restrictive cardiomyopathies are caused by mutations in sarcomeric genes such as cardiac troponin I, and less commonly by mutations in Desmin ( DES ) and Filamin C ( FLNC ) ( 7 ). It is worth noting that although cardiomyopathies are classified based on phenotypes manifested in the general population, the pathogenic mechanisms and phenotypic features among the various types of cardiomyopathies can overlap to a significant degree.…”

Section: Introductionmentioning

confidence: 99%

The role of noncoding genetic variants in cardiomyopathy

Htet,

Lei,

Bajpayi

et al. 2023

Front. Cardiovasc. Med.

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Cardiomyopathies remain one of the leading causes of morbidity and mortality worldwide. Environmental risk factors and genetic predisposition account for most cardiomyopathy cases. As with all complex diseases, there are significant challenges in the interpretation of the molecular mechanisms underlying cardiomyopathy-associated genetic variants. Given the technical improvements and reduced costs of DNA sequence technologies, an increasing number of patients are now undergoing genetic testing, resulting in a continuously expanding list of novel mutations. However, many patients carry noncoding genetic variants, and although emerging evidence supports their contribution to cardiac disease, their role in cardiomyopathies remains largely understudied. In this review, we summarize published studies reporting on the association of different types of noncoding variants with various types of cardiomyopathies. We focus on variants within transcriptional enhancers, promoters, intronic sites, and untranslated regions that are likely associated with cardiac disease. Given the broad nature of this topic, we provide an overview of studies that are relatively recent and have sufficient evidence to support a significant degree of causality. We believe that more research with additional validation of noncoding genetic variants will provide further mechanistic insights on the development of cardiac disease, and noncoding variants will be increasingly incorporated in future genetic screening tests.

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Genetic Insights into Primary Restrictive Cardiomyopathy

Cited by 26 publications

References 232 publications

Focus on Paediatric Restrictive Cardiomyopathy: Frequently Asked Questions

Focus on Paediatric Restrictive Cardiomyopathy: Frequently Asked Questions

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

The role of noncoding genetic variants in cardiomyopathy

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