Circulation: Genomic and Precision Medicine最新文献

{"title":"Cardiac Sarcoidosis Mimickers: Genetic Testing in Undifferentiated Inflammatory Cardiomyopathies.","authors":"Matteo Castrichini, Kolade M Agboola, Hridyanshu Vyas, Omar F Abou Ezzeddine, Konstantinos C Siontis, John R Giudicessi, Andrew N Rosenbaum, Naveen L Pereira","doi":"10.1161/CIRCGEN.123.004099","DOIUrl":"10.1161/CIRCGEN.123.004099","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9746813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of Rapid Genome Sequencing for Critically Ill Infants With Complex Congenital Heart Disease.","authors":"Thomas Hays,&nbsp;Rebecca Hernan,&nbsp;Michele Disco,&nbsp;Emily L Griffin,&nbsp;Nimrod Goldshtrom,&nbsp;Diana Vargas,&nbsp;Ganga Krishnamurthy,&nbsp;Miles Bomback,&nbsp;Atteeq U Rehman,&nbsp;Amanda T Wilson,&nbsp;Saurav Guha,&nbsp;Shruti Phadke,&nbsp;Volkan Okur,&nbsp;Dino Robinson,&nbsp;Vanessa Felice,&nbsp;Avinash Abhyankar,&nbsp;Vaidehi Jobanputra,&nbsp;Wendy K Chung","doi":"10.1161/CIRCGEN.122.004050","DOIUrl":"10.1161/CIRCGEN.122.004050","url":null,"abstract":"<p><strong>Background: </strong>Rapid genome sequencing (rGS) has been shown to improve care of critically ill infants. Congenital heart disease (CHD) is a leading cause of infant mortality and is often caused by genetic disorders, yet the utility of rGS has not been prospectively studied in this population.</p><p><strong>Methods: </strong>We conducted a prospective evaluation of rGS to improve the care of infants with complex CHD in our cardiac neonatal intensive care unit.</p><p><strong>Results: </strong>In a cohort of 48 infants with complex CHD, rGS diagnosed 14 genetic disorders in 13 (27%) individuals and led to changes in clinical management in 8 (62%) cases with diagnostic results. These included 2 cases in whom genetic diagnoses helped avert intensive, futile interventions before cardiac neonatal intensive care unit discharge, and 3 cases in whom eye disease was diagnosed and treated in early childhood.</p><p><strong>Conclusions: </strong>Our study provides the first prospective evaluation of rGS for infants with complex CHD to our knowledge. We found that rGS diagnosed genetic disorders in 27% of cases and led to changes in management in 62% of cases with diagnostic results. Our model of care depended on coordination between neonatologists, cardiologists, surgeons, geneticists, and genetic counselors. These findings highlight the important role of rGS in CHD and demonstrate the need for expanded study of how to implement this resource to a broader population of infants with CHD.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary Polygenic Scores of Low-Density Lipoprotein Cholesterol and Coronary Artery Disease Predict Coronary Atherosclerosis in Adolescents and Young Adults.","authors":"Rodrigo Guarischi-Sousa, Elias Salfati, Pik Fang Kho, Kruthika R Iyer, Austin T Hilliard, David M Herrington, Philip S Tsao, Shoa L Clarke, Themistocles L Assimes","doi":"10.1161/CIRCGEN.122.004047","DOIUrl":"10.1161/CIRCGEN.122.004047","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/30/hcg-16-480.PMC10581412.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9756486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Childhood Hypertrophic Cardiomyopathy Caused by Beta-Myosin Heavy Chain Variants Is Associated With a More Obstructive but Less Arrhythmogenic Phenotype Than Myosin-Binding Protein C Disease.","authors":"Gabrielle Norrish, Vidthya Kadirrajah, Ella Field, Kathleen Dady, Jennifer Tollit, Karen McLeod, Ruth McGowan, Elena Cervi, Juan Pablo Kaski","doi":"10.1161/CIRCGEN.123.004118","DOIUrl":"10.1161/CIRCGEN.123.004118","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9702200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype of ASDs Associated With 4p16 Risk Locus and Novel Genome-Wide Associations of ASD Patients in the Finnish Population.","authors":"Valtteri Muroke,&nbsp;Mikko Jalanko,&nbsp;Sanni Ruotsalainen,&nbsp;Markus Perola,&nbsp;Emmi Helle,&nbsp;Juha Sinisalo","doi":"10.1161/CIRCGEN.123.004070","DOIUrl":"10.1161/CIRCGEN.123.004070","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Efficacy of Lipid-Lowering Drug Targets Is Not Entirely Explained by Apolipoprotein B Reduction: Mendelian Randomization Evidence.","authors":"Dipender Gill,&nbsp;Benjamin Woolf,&nbsp;Loukas Zagkos,&nbsp;Héléne T Cronjé,&nbsp;Ioanna Tzoulaki","doi":"10.1161/CIRCGEN.123.004204","DOIUrl":"10.1161/CIRCGEN.123.004204","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9990902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contiguous Gene Deletion of Chromosome 15q25.2q25.3 in Biallelic <i>ALPK3</i>-Related Cardiomyopathy: Novel Insights Into Phenotypic Presentation and Variant Spectrum.","authors":"Laura A Grutters,&nbsp;Jolien S Klein Wassink-Ruiter,&nbsp;Trijnie Dijkhuizen,&nbsp;Hessel P Nijenhuis,&nbsp;Jan D H Jongbloed,&nbsp;Johanna C Herkert","doi":"10.1161/CIRCGEN.123.004094","DOIUrl":"10.1161/CIRCGEN.123.004094","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10159745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Cost High-Throughput Genotyping for Diagnosing Familial Hypercholesterolemia.","authors":"Shirin Ibrahim,&nbsp;Jeroen van Rooij,&nbsp;Annemieke J M H Verkerk,&nbsp;Jard de Vries,&nbsp;Linda Zuurbier,&nbsp;Joep Defesche,&nbsp;Jorge Peter,&nbsp;Willemijn A M Schonck,&nbsp;Bahar Sedaghati-Khayat,&nbsp;G Kees Hovingh,&nbsp;André G Uitterlinden,&nbsp;Erik S G Stroes,&nbsp;Laurens F Reeskamp","doi":"10.1161/CIRCGEN.123.004103","DOIUrl":"10.1161/CIRCGEN.123.004103","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a common but underdiagnosed genetic disorder characterized by high low-density lipoprotein cholesterol levels and premature cardiovascular disease. Current sequencing methods to diagnose FH are expensive and time-consuming. In this study, we evaluated the accuracy of a low-cost, high-throughput genotyping array for diagnosing FH.</p><p><strong>Methods: </strong>An Illumina Global Screening Array was customized to include probes for 636 variants, previously classified as FH-causing variants. First, its theoretical coverage was assessed in all FH variant carriers diagnosed through next-generation sequencing between 2016 and 2022 in the Netherlands (n=1772). Next, the performance of the array was validated in another sample of FH variant carriers previously identified in the Dutch FH cascade screening program (n=1268).</p><p><strong>Results: </strong>The theoretical coverage of the array for FH-causing variants was 91.3%. Validation of the array was assessed in a sample of 1268 carriers of whom 1015 carried a variant in <i>LDLR</i>, 250 in <i>APOB</i>, and 3 in <i>PCSK9</i>. The overall sensitivity was 94.7% and increased to 98.2% after excluding participants with variants not included in the array design. Copy number variation analysis yielded a 89.4% sensitivity. In 18 carriers, the array identified a total of 19 additional FH-causing variants. Subsequent DNA analysis confirmed 5 of the additionally identified variants, yielding a false-positive result in 16 subjects (1.3%).</p><p><strong>Conclusions: </strong>The FH genotyping array is a promising tool for genetically diagnosing FH at low costs and has the potential to greatly increase accessibility to genetic testing for FH. Continuous customization of the array will further improve its performance.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Contribution to End-Stage Cardiomyopathy Requiring Heart Transplantation.","authors":"Yuri Kim, Oddný Brattberg Gunnarsdóttir, Anissa Viveiros, Daniel Reichart, Daniel Quiat, Jon A L Willcox, Hao Zhang, Huachen Chen, Justin J Curran, Daniel H Kim, Simon Urschel, Barbara McDonough, Joshua Gorham, Steven R DePalma, Jonathan G Seidman, Christine E Seidman, Gavin Y Oudit","doi":"10.1161/CIRCGEN.123.004062","DOIUrl":"10.1161/CIRCGEN.123.004062","url":null,"abstract":"<p><strong>Background: </strong>Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to define causes are often abandoned, resulting in a diagnosis of end-stage idiopathic cardiomyopathy. We studied whether DNA sequence analyses could identify unrecognized causes of end-stage nonischemic cardiomyopathy requiring heart transplantation and whether the prevalence of genetic causes differed from ambulatory cardiomyopathy cases.</p><p><strong>Methods: </strong>We performed whole exome and genome sequencing of 122 explanted hearts from 101 adult and 21 pediatric patients with idiopathic cardiomyopathy from a single center. Data were analyzed for pathogenic/likely pathogenic variants in nuclear and mitochondrial genomes and assessed for nonhuman microbial sequences. The frequency of damaging genetic variants was compared among cardiomyopathy cohorts with different clinical severity.</p><p><strong>Results: </strong>Fifty-four samples (44.3%) had pathogenic/likely pathogenic cardiomyopathy gene variants. The frequency of pathogenic variants was similar in pediatric (42.9%) and adult (43.6%) samples, but the distribution of mutated genes differed (<i>P</i>=8.30×10^-4). The prevalence of causal genetic variants was significantly higher in end-stage than in previously reported ambulatory adult dilated cardiomyopathy cases (<i>P</i><0.001). Among remaining samples with unexplained causes, no damaging mitochondrial variants were identified, but 28 samples contained parvovirus genome sequences, including 2 samples with 6- to 9-fold higher levels than the overall mean levels in other samples.</p><p><strong>Conclusions: </strong>Pathogenic variants and viral myocarditis were identified in 45.9% of patients with unexplained end-stage cardiomyopathy. Damaging gene variants are significantly more frequent among transplant compared with patients with ambulatory cardiomyopathy. Genetic analyses can help define cause of end-stage cardiomyopathy to guide management and risk stratification of patients and family members.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyopathy in Asian Cohorts: Genetic and Epigenetic Insights.","authors":"Konstanze Tan,&nbsp;Roger Foo,&nbsp;Marie Loh","doi":"10.1161/CIRCGEN.123.004079","DOIUrl":"10.1161/CIRCGEN.123.004079","url":null,"abstract":"<p><p>Previous studies on cardiomyopathies have been particularly valuable for clarifying pathological mechanisms in heart failure, an etiologically heterogeneous disease. In this review, we specifically focus on cardiomyopathies in Asia, where heart failure is particularly pertinent. There has been an increase in prevalence of cardiomyopathies in Asia, in sharp contrast with the decline observed in Western countries. Indeed, important disparities in cardiomyopathy incidence, clinical characteristics, and prognosis have been reported in Asian versus White cohorts. These have been accompanied by emerging descriptions of a distinct rare and common genetic basis for disease among Asian cardiomyopathy patients marked by an increased burden of variants with uncertain significance, reclassification of variants deemed pathogenic based on evidence from predominantly White cohorts, and the discovery of Asian-specific cardiomyopathy-associated loci with underappreciated pathogenicity under conventional classification criteria. Findings from epigenetic studies of heart failure, particularly DNA methylation studies, have complemented genetic findings in accounting for the phenotypic variability in cardiomyopathy. Though extremely limited, findings from Asian ancestry-focused DNA methylation studies of cardiomyopathy have shown potential to contribute to general understanding of cardiomyopathy pathophysiology by proposing disease and cause-relevant pathophysiological mechanisms. We discuss the value of multiomics study designs incorporating genetic, methylation, and transcriptomic information for future DNA methylation studies in Asian cardiomyopathy cohorts to yield Asian ancestry-specific insights that will improve risk stratification in the Asian population.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}