Circulation: Cardiovascular Genetics最新文献

{"title":"Technical Advances for the Clinical Genomic Evaluation of Sudden Cardiac Death: Verification of Next-Generation Sequencing Panels for Hereditary Cardiovascular Conditions Using Formalin-Fixed Paraffin-Embedded Tissues and Dried Blood Spots.","authors":"Linnea M Baudhuin,&nbsp;Charles Leduc,&nbsp;Laura J Train,&nbsp;Rajeswari Avula,&nbsp;Michelle L Kluge,&nbsp;Katrina E Kotzer,&nbsp;Peter T Lin,&nbsp;Michael J Ackerman,&nbsp;Joseph J Maleszewski","doi":"10.1161/CIRCGENETICS.117.001844","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001844","url":null,"abstract":"<p><strong>Background: </strong>Postmortem genetic testing for heritable cardiovascular (CV) disorders is often lacking because ideal specimens (ie, whole blood) are not retained routinely at autopsy. Formalin-fixed paraffin-embedded tissue (FFPET) is ubiquitously collected at autopsy, but DNA quality hampers its use with traditional sequencing methods. Targeted next-generation sequencing may offer the ability to circumvent such limitations, but a method has not been previously described. The primary aim of this study was to develop and evaluate the use of FFPET for heritable CV disorders via next-generation sequencing.</p><p><strong>Methods and results: </strong>Nineteen FFPET (heart) and blood (whole blood or dried blood spot) specimens underwent targeted next-generation sequencing using a custom panel of 101 CV-associated genes. Nucleic acid yield and quality metrics were evaluated in relation to FFPET specimen age (6 months to 15 years; n=14) and specimen type (FFPET versus whole blood and dried blood spot; n=12). Four FFPET cases with a clinical phenotype of heritable CV disorder were analyzed. Accuracy and precision were 100% concordant between all sample types, with read depths >100× for most regions tested. Lower read depth, as low as 40×, was occasionally observed with FFPET and dried blood spot. High-quality DNA was obtained from FFPET samples as old as 15 years. Genomic analysis of FFPET from the 4 phenotype-positive/genotype unknown cases all revealed putative disease-causing variants.</p><p><strong>Conclusions: </strong>Similar performance characteristics were observed for next-generation sequencing of FFPET, whole blood, and dried blood spot in the evaluation of inherited CV disorders. Although blood is preferable for genetic analyses, this study offers an alternative when only FFPET is available.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin Effects on Metabolic Profiles: Data From the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial).","authors":"Daniel Kofink,&nbsp;Ruben N Eppinga,&nbsp;Wiek H van Gilst,&nbsp;Stephan J L Bakker,&nbsp;Robin P F Dullaart,&nbsp;Pim van der Harst,&nbsp;Folkert W Asselbergs","doi":"10.1161/CIRCGENETICS.117.001759","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001759","url":null,"abstract":"<p><strong>Background: </strong>Statins lower cholesterol by inhibiting HMG-CoA reductase, the rate-limiting enzyme of the metabolic pathway that produces cholesterol and other isoprenoids. Little is known about their effects on metabolite and lipoprotein subclass profiles. We, therefore, investigated the molecular changes associated with pravastatin treatment compared with placebo administration using a nuclear magnetic resonance-based metabolomics platform.</p><p><strong>Methods and results: </strong>We performed metabolic profiling of 231 lipoprotein and metabolite measures in the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial) study, a placebo-controlled randomized clinical trial designed to test the effects of pravastatin (40 mg once daily) on cardiovascular risk. Metabolic profiles were assessed at baseline and after 3 months of treatment. Pravastatin lowered low-density lipoprotein cholesterol (change in SD units [95% confidence interval]: -1.01 [-1.14, -0.88]), remnant cholesterol (change in SD units [95% confidence interval]: -1.03 [-1.17, -0.89]), and apolipoprotein B (change in SD units [95% confidence interval]: -0.98 [-1.11, -0.86]) with similar effect magnitudes. In addition, pravastatin globally lowered levels of lipoprotein subclasses, with the exception of high-density lipoprotein subclasses, which displayed a more heterogeneous response pattern. The lipid-lowering effect of pravastatin was accompanied by selective changes in lipid composition, particularly in the cholesterol content of very-low-density lipoproteinparticles. In addition, pravastatin reduced levels of several fatty acids but had limited effects on fatty acid ratios.</p><p><strong>Conclusions: </strong>These randomized clinical trial data demonstrate the widespread effects of pravastatin treatment on lipoprotein subclass profiles and fatty acids.</p><p><strong>Clinical trial registration: </strong>URL: http://www.clinicaltrials.gov. Unique identifier: NCT03073018.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-Based Risk Stratification for Cardiac Disorders in <i>LMNA</i> Mutation Carriers.","authors":"Suguru Nishiuchi,&nbsp;Takeru Makiyama,&nbsp;Takeshi Aiba,&nbsp;Kenzaburo Nakajima,&nbsp;Sayako Hirose,&nbsp;Hirohiko Kohjitani,&nbsp;Yuta Yamamoto,&nbsp;Takeshi Harita,&nbsp;Mamoru Hayano,&nbsp;Yimin Wuriyanghai,&nbsp;Jiarong Chen,&nbsp;Kenichi Sasaki,&nbsp;Nobue Yagihara,&nbsp;Taisuke Ishikawa,&nbsp;Kenji Onoue,&nbsp;Nobuyuki Murakoshi,&nbsp;Ichiro Watanabe,&nbsp;Kimie Ohkubo,&nbsp;Hiroshi Watanabe,&nbsp;Seiko Ohno,&nbsp;Takahiro Doi,&nbsp;Satoshi Shizuta,&nbsp;Tohru Minamino,&nbsp;Yoshihiko Saito,&nbsp;Yasushi Oginosawa,&nbsp;Akihiko Nogami,&nbsp;Kazutaka Aonuma,&nbsp;Kengo Kusano,&nbsp;Naomasa Makita,&nbsp;Wataru Shimizu,&nbsp;Minoru Horie,&nbsp;Takeshi Kimura","doi":"10.1161/CIRCGENETICS.116.001603","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.116.001603","url":null,"abstract":"<p><strong>Background: </strong>Mutations in <i>LMNA</i> (<i>lamin A/C</i>), which encodes lamin A and C, typically cause age-dependent cardiac phenotypes, including dilated cardiomyopathy, cardiac conduction disturbance, atrial fibrillation, and malignant ventricular arrhythmias. Although the type of <i>LMNA</i> mutations have been reported to be associated with susceptibility to malignant ventricular arrhythmias, the gene-based risk stratification for cardiac complications remains unexplored.</p><p><strong>Methods and results: </strong>The multicenter cohort included 77 <i>LMNA</i> mutation carriers from 45 families; cardiac disorders were retrospectively analyzed. The mean age of patients when they underwent genetic testing was 45±17, and they were followed for a median 49 months. Of the 77 carriers, 71 (92%) were phenotypically affected and showed cardiac conduction disturbance (81%), low left ventricular ejection fraction (<50%; 45%), atrial arrhythmias (58%), and malignant ventricular arrhythmias (26%). During the follow-up period, 9 (12%) died, either from end-stage heart failure (n=7) or suddenly (n=2). Genetic analysis showed truncation mutations in 58 patients from 31 families and missense mutations in 19 patients from 14 families. The onset of cardiac disorders indicated that subjects with truncation mutations had an earlier occurrence of cardiac conduction disturbance and low left ventricular ejection fraction, than those with missense mutations. In addition, the truncation mutation was found to be a risk factor for the early onset of cardiac conduction disturbance and the occurrence of atrial arrhythmias and low left ventricular ejection fraction, as estimated using multivariable analyses.</p><p><strong>Conclusions: </strong>The truncation mutations were associated with manifestation of cardiac phenotypes in <i>LMNA</i>-related cardiomyopathy, suggesting that genetic analysis might be useful for diagnosis and risk stratification.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.116.001603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>MYH7</i> Rare Variant in a Family With Double-Chambered Left Ventricle.","authors":"Jing Wang,&nbsp;Xin Zhang,&nbsp;Xi Wang,&nbsp;Chuchu Wang,&nbsp;Fangyun Wang,&nbsp;Binbin Wang","doi":"10.1161/CIRCGENETICS.117.001729","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001729","url":null,"abstract":"An 11-year-old boy was admitted to hospital with symptoms of nausea, edema, fatigability, and inability to lie down, which slowly developed over the past 4 months. Transthoracic echocardiography and an ECG were performed and showed the diagnosis of double-chambered left ventricle (DCLV).\u0000\u0000A physical examination showed protrusion of the precordium, soft heart sounds, cardiomegaly, a grade 3/6 systolic murmur at the cardiac apex, and enlargement of the liver to 3 cm below the right costal margin. ECG showed a sinus rhythm with left ventricular hypertrophy. Transthoracic echocardiography demonstrated that the left ventricle was divided into basal and apical chambers by an incomplete fibromuscular septum (Figure 1A). The basal chamber, which communicated with the left atrium and the normally positioned aorta, was severely enlarged with an end-diastolic diameter of 80.7 mm. This chamber was abnormally configured to the shape of a ball. The basal and midventricular septum expanded toward the right ventricle. The left ventricular wall and septum had impaired contraction with severe reduction of the left ventricular ejection fraction to 35%. Systolic pressure of the 2 chambers was similar, and the diameter of communication between them was 16.0 mm. There was thinning of the wall of the apical chamber. A DCLV was also shown by cardiac magnetic resonance imaging (Figure 1B). The patient’s ECG showed sinus rhythm, T-wave changes, and enlargement of the left ventricle and left atrium (Figure 1C).\u0000\u0000\u0000\u0000Figure 1. \u0000Clinical feathers of the DCLV proband. A , Apical 4-chamber view of transthoracic echocardiography of the proband. B , Cardiac magnetic resonance imaging shows the diagnosis. C , ECG result of the proband. white arrow, fibromuscular septum. LA indicates left atrium; LV1, basal chamber of the left ventricle; LV2, apical chamber of the left ventricle; RA, right atrium; …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001729","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four-Generation Family With Ebstein Anomaly Highlights Future Challenges in Congenital Heart Disease Genetics.","authors":"David S Winlaw,&nbsp;Sally L Dunwoodie,&nbsp;Edwin P Kirk","doi":"10.1161/CIRCGENETICS.117.001967","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001967","url":null,"abstract":"Mercer et al1 describe a family in which a missense variant in Filamin A ( FLNA ) segregates with Ebstein anomaly. This is a syndromal form of congenital heart disease (CHD) in that affected individuals have craniofacial and musculoskeletal anomalies, as well as keloid scarring and oligodontia. Clinically, affected family members had no apparent neurological involvement, although cranial imaging was not reported. Overall, the phenotype is clearly in a continuum with other FLNA -associated disorders including otopalatodigital syndrome (OPD1 and OPD2) and Melnick–Needles syndrome. However, this represents a new addition to the stable phenotypes linked to FLNA , with the cardiac features being particularly noteworthy.\u0000\u0000See Article by Mercer et al \u0000\u0000Such families are a unique resource in expanding our knowledge of causal genes and mechanisms in CHD. The unfolding of this story (some of the family had previously been screened for NKX2-5 and MYH7 mutations in a previous era) over some 25 years, and 4 generations are testament to the persistence of the authors, as well as the effectiveness of modern sequencing technology. It also illustrates the power of the phenotype to illuminate the genotype. Previously, FLNA had been associated with cardiac valvular disease (not including Ebstein anomaly) …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lamin A/C Cardiomyopathy: Cutting Edge to Personalized Medicine.","authors":"Gianfranco Sinagra,&nbsp;Matteo Dal Ferro,&nbsp;Marco Merlo","doi":"10.1161/CIRCGENETICS.117.002004","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.002004","url":null,"abstract":"Dilated cardiomyopathy (DCM) has a prevalence currently estimated as high as 1:250/1:500 and affects mostly young working-age people.1 Despite recent advances in medical and device therapies, the prognosis of DCM has been significantly improved in last decades,2 heart failure or sudden deaths, hospitalizations, need of heart transplantation, and morbidity rates remain relatively high and unpredictable.3 Consequently, more accurate risk stratification is still a critical and unmet issue.\u0000\u0000See Article by Nishiuchi et al \u0000\u0000Genetic characterization is gaining a prominent role in personalizing DCM prognostication. In the past, the proportion of patients with genetically determined DCM has been substantially underestimated because of variable clinical presentation, incomplete disease penetrance, and the lack of specific phenotypes. However, recent series using genetic screening suggest that ≤40% of DCM is genetically determined.4 To date, >50 genes have been implicated in DCM.5 Nevertheless, genotype–phenotype interactions still represent a challenge for translational research and cardiology. In fact, genotype information often does not have a known corresponding specific clinical phenotype. In particular, the clinical management of relatives carrying likely or possibly pathogenic mutations without overt phenotype remains currently uncertain in the specific setting of DCM.\u0000\u0000In this field, LMNA had always represented the more investigated gene with several prospective and retrospective studies.6–8 Because of the association with a relatively high incidence of sudden cardiac death or major ventricular arrhythmias, even before development of systolic left ventricular dysfunction, LMNA mutations represent the only genetic background in DCM that change clinical choices such as the implantable cardioverter defibrillator therapy in …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.002004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Proteomics for Epidemiology: Increasing Throughput With Standard-Flow Rates.","authors":"Xiaoke Yin,&nbsp;Ferheen Baig,&nbsp;Eloi Haudebourg,&nbsp;Richard T Blankley,&nbsp;Tejas Gandhi,&nbsp;Sebastian Müller,&nbsp;Lukas Reiter,&nbsp;Helmut Hinterwirth,&nbsp;Raimund Pechlaner,&nbsp;Sotirios Tsimikas,&nbsp;Peter Santer,&nbsp;Johann Willeit,&nbsp;Stefan Kiechl,&nbsp;Joseph L Witztum,&nbsp;Anthony Sullivan,&nbsp;Manuel Mayr","doi":"10.1161/CIRCGENETICS.117.001808","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001808","url":null,"abstract":"<p><strong>Background: </strong>Mass spectrometry is selective and sensitive, permitting routine quantification of multiple plasma proteins. However, commonly used nanoflow liquid chromatography (LC) approaches hamper sample throughput, reproducibility, and robustness. For this reason, most publications using plasma proteomics to date are small in study size.</p><p><strong>Methods and results: </strong>Here, we tested a standard-flow LC mass spectrometry (MS) method using multiple reaction monitoring for the application to large epidemiological cohorts. We have reduced the LC-MS run time to almost a third of the nanoflow LC-MS approach. On the basis of a comparison of the quantification of 100 plasma proteins in >1500 LC-MS runs, the SD range of the retention time during continuous operation was substantially lower with the standard-flow LC-MS (<0.05 minutes) compared with the nanoflow LC-MS method (0.26-0.44 minutes). In addition, the standard-flow LC method also offered less variation in protein measurements. However, 5× more sample volume was required to achieve similar sensitivity. Two different commercial multiple reaction monitoring kits and an antibody-based multiplexing kit were used to compare the apolipoprotein measurements in a subset of samples. In general, good agreement was observed between the 2 multiple reaction monitoring kits, but some of the multiple reaction monitoring-based measurements differed from antibody-based assays.</p><p><strong>Conclusions: </strong>The multiplexing capability of LC-MS combined with a standard-flow method increases throughput and reduces the costs of large-scale protein measurements in epidemiological cohorts, but protein rather than peptide standards will be required for defined absolute proteoform quantification.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"News From the Heart Natriuretic System.","authors":"Ines Armando","doi":"10.1161/CIRCGENETICS.117.002011","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.002011","url":null,"abstract":"Renal and nonrenal mechanisms are involved in the long-term regulation of blood pressure that is dependent on a precise balance among humoral agents and vasoconstrictor and vasodilator hormones and other factors that act to increase or decrease renal sodium transport. These imply a complex interaction between natriuretic and antinatriuretic systems. The dysregulation of ion transport intrinsic and extrinsic to the kidney has been proposed to cause essential hypertension.\u0000\u0000See Article by Salo et al \u0000\u0000An important natriuretic system is that comprising the cardiac hormones, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP), playing a critical role in the reduction of blood pressure and cardiac disorders with relevance to renal and cardiovascular homeostasis. ANP is synthesized and stored in the atrial granules as a prohormone with 126 amino acids, proANP. BNP is deglycosylated from a 108-amino acid prohormone, proBNP, and further processed into an amino …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.002011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>FLNC</i> (Filamin-C): A New(er) Player in the Field of Genetic Cardiomyopathies.","authors":"Andreas Brodehl,&nbsp;Anna Gaertner-Rommel,&nbsp;Hendrik Milting","doi":"10.1161/CIRCGENETICS.117.001959","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001959","url":null,"abstract":"In 1990, the Seidman group identified the first pathogenic cardiomyopathy mutation in a large 4-generation family, where several members were affected by hypertrophic cardiomyopathy.1 Since this first report, the number of genes and mutations associated with different cardiomyopathies is increasing from year to year. Currently, mutations in >170 genes associated with different cardiomyopathies, channelopathies, or syndromes with cardiac involvement are described. The huge number of different genes and mutations involved in cardiomyopathies limited routine genetic diagnostics for a long time. For example, Sanger sequencing of TTN, encoding the giant sarcomere protein titin, was difficult, expensive, and time consuming and limited the routine genetic diagnosis.2,3 Therefore, it was not surprising that the development of efficient next-generation sequencing technology pushed also the genetic diagnostics of cardiovascular diseases. Today, cardiovascular next-generation sequencing techniques are implemented in many diagnostic laboratories.4 The availability of next-generation sequencing technology has in the meantime provided the important insight that cardiomyopathies are remarkable heterogeneous disorders with different expressivity and penetrance. The challenges for the future remain the identification of phenotype–genotype relationships and consequences of genotyping for the development of personalized therapies.\u0000\u0000See Article Tucker and McLellan et al \u0000\u0000In this context, the contribution of a genetic pathogenesis to restrictive cardiomyopathy (RCM) is incompletely understood. Besides genetic factors, RCM might be a secondary cardiomyopathy and part of a systemic disease like the mineralization disorder pseudoxanthoma elasticum or cardiac amyloidosis. First mutations associated with familial RCM were identified in TNNI3 by the research group of William McKenna in 2003.5 During the …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001959","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35318161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1161/HCG.0000000000000039","DOIUrl":"https://doi.org/10.1161/HCG.0000000000000039","url":null,"abstract":"","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":"e000039"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/HCG.0000000000000039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36849920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}