Circulation: Genomic and Precision Medicine最新文献

{"title":"VEGFA Stop-Gained Variant Deteriorates Cardiac Remodeling in Myocardial Infarction.","authors":"Zhongxiang Chen, Diqi Zhu, Kaa Seng Lai, Yiwei Chen, Yuqing Hu, Yabo Fang, Zihang Yan, Beibei Hu, Zhen Zhang, Min Zhang, Fen Li","doi":"10.1161/CIRCGEN.124.004879","DOIUrl":"https://doi.org/10.1161/CIRCGEN.124.004879","url":null,"abstract":"<p><strong>Background: </strong>A sustained dosage of VEGFA (vascular endothelial growth factor A) is crucial for angiogenesis in both homeostasis and cardiovascular diseases. CUG-initiated alternative translation is a conserved mechanism for producing mature VEGFA. Genetic surveys have identified stop-gained variants predicted to prematurely terminate CUG-initiated translation without affecting ATG-initiated translation. However, the impacts of these variants on the vasculature in steady-state and disease conditions remain unknown.</p><p><strong>Methods: </strong>Using CRISPR/Cas9 genome editing, we established the <i>Vegfa</i>^{<i>Q150X/Q150</i>} allele (Q150X), a mouse genetic model that mimics the human VEGFA stop-gained variant. The effects of this variant were tested in both adult homeostatic conditions and the acute myocardial infarction (MI) model. We analyzed and quantified cardiac vasculature structure using immunofluorescence and light-sheet imaging. Furthermore, we characterized cellular heterogeneity, cell-cell interactions, and gene regulation using single-nucleus RNA sequencing, as well as cell type-specific transcriptomics and epigenomics.</p><p><strong>Results: </strong>Homozygous mice carrying the stop-gained variant were viable. VEGFA dosage was reduced to 70% in the Q150X homeostatic heart, with no significant alteration in cardiac function or vasculature. In the MI model, VEGFA dosage in Q150X was reduced to about 40% within the first week post-infarction, leading to functional deterioration in the post-MI hearts. Significant changes in cellular composition were observed 3 days post-MI. In particular, endothelial cells in Q150X diverged into a state that showed a higher level of hypoxia stress, an elevated inflammatory response, and increased extracellular matrix secretion. In addition, we observed an increase in Nppb⁺ stressed cardiomyocytes in both 3 days post-MI and homeostasis. Finally, proinflammatory macrophages, neutrophils, and Cd8⁺T cells were enriched in the ischemic zone of Q150X hearts.</p><p><strong>Conclusions: </strong>CUG-initiated translation contributes significantly to the production of mature VEGFA in ischemic hearts. VEGFA dosage is critical in determining the cellular microenvironment during ischemic injury.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004879"},"PeriodicalIF":6.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658594","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":"Calibrated Functional Data Decrease Clinical Uncertainty for <i>KCNH2</i>-Related Long-QT Syndrome.","authors":"Chai-Ann Ng, Matthew J O'Neill, Samskruthi R Padigepati, Yi-Lee Ting, Flavia M Facio, Matteo Vatta, Sarah R Poll, Jason A Reuter, Jamie I Vandenberg, Brett M Kroncke","doi":"10.1161/CIRCGEN.125.005204","DOIUrl":"https://doi.org/10.1161/CIRCGEN.125.005204","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005204"},"PeriodicalIF":6.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658593","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":"Cardiac Troponin C E135A Variant Impairs Myofilament Response to PKA Phosphorylation and Is Associated With Autosomal Dominant Dilated Cardiomyopathy With Diastolic Dysfunction.","authors":"Maicon Landim-Vieira, Robin M Perelli, Michelle Rodriguez-Garcia, Vivek P Jani, Ronnie C Chastain, Joshua H Lamar, Ellen Mines, Gwimoon Seo, Aurelia Araujo Fernandes, Bjorn Knollmann, Michael P Carboni, Stephen P Chelko, Vitold E Galkin, P Bryant Chase, Jose Renato Pinto, Andrew P Landstrom","doi":"10.1161/CIRCGEN.124.004720","DOIUrl":"https://doi.org/10.1161/CIRCGEN.124.004720","url":null,"abstract":"<p><strong>Background: </strong>Dilated cardiomyopathy (DCM) is a heart muscle disease in which the left ventricle is enlarged, resulting in systolic dysfunction. Pathogenic variants in genes encoding proteins involved in cardiac contractility, cytoskeleton structure, and Ca²⁺ handling have been associated with DCM. <i>TNNC1</i> (cTnC [cardiac troponin C]) variants are implicated in DCM, hypertrophic, and restrictive cardiomyopathies. Unlike other sarcomere genes, most reports of <i>TNNC1</i> variants lack segregation or pedigree data, partly because the majority of the variants described, to date, have been reported as de novo. Therefore, a critical need is warranted to further understand the mechanisms by which <i>TNNC1</i> variants could impact myofilament function, especially in response to PKA (protein kinase A)-mediated phosphorylation as this posttranslational modification modulates sarcomere function in response to β-adrenergic stimulation.</p><p><strong>Methods: </strong>Probands with the novel <i>TNNC1</i>-c.404A>C variant (cTnC-E135A) and family members were identified and consented. cTnC-depleted donor human cardiac muscle preparations were reconstituted with recombinant exogenous human cTnC-E135A. Steady-state isometric force and crossbridge kinetics were measured before and after PKA incubation. We used in silico modeling to further investigate crossbridge cycling kinetics.</p><p><strong>Results: </strong>We identified a multigenerational family carrying the <i>TNNC1</i>-c.404A>C variant with autosomal dominant DCM with both systolic and diastolic dysfunctions. Using reconstituted human cardiac muscle preparations, we showed that the cTnC-E135A abolishes the myofilament response to PKA-mediated phosphorylation. Furthermore, in silico mathematical modeling showed that this variant affects crossbridge kinetics by decreasing both Ca²⁺ <i>k</i>_OFF-rate constant and myosin detachment rate, which could result in increased ventricular stiffness and reduced ejection fraction.</p><p><strong>Conclusions: </strong>Our clinical and genetics data, combined with the in silico modeling and functional assays, suggest that cTnC-E135A is associated with DCM and disrupts kinetics of Ca²⁺ and crossbridge cycling by abolishing the myofilament response to PKA phosphorylation.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004720"},"PeriodicalIF":6.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648737","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":"Molecular Phenogroups in Heart Failure: Large-Scale Proteomics in a Population-Based Cohort.","authors":"Carolina G Downie, Joseph J Shearer, Kayode O Kuku, Suzette J Bielinski, Jorge R Kizer, Bruce M Psaty, Jungnam Joo, Véronique L Roger","doi":"10.1161/CIRCGEN.124.004953","DOIUrl":"https://doi.org/10.1161/CIRCGEN.124.004953","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) is a heterogeneous syndrome with high mortality. The need for a new taxonomy of HF is recognized; up to now, such phenomapping efforts have primarily used clinical data. Proteomics offers potential for more precise phenotypic identification and mechanistic insights. However, few phenomapping studies have used this approach, and all have focused on targeted cardiovascular proteomics panels and a restricted HF ejection fraction group.</p><p><strong>Methods: </strong>We measured over 7000 plasma proteins in a population-based cohort of 1351 patients with HF, used k-means clustering to identify distinct phenogroups, and compared their clinical characteristics and all-cause mortality.</p><p><strong>Results: </strong>Three proteomics-defined phenogroups were identified, with substantial differences in survival (phenogroup 1 5-year survival probability, 65% [95% CI, 61%-68%]; phenogroup 2, 45% [40%-51%]; phenogroup 3, 26% [22%-30%]), independent of clinical characteristics. Phenogroups also exhibited differences in several measures suggesting poorer health, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), kidney function, and Meta-Analysis Global Group in Chronic Heart Failure scores, but did not differ by ejection fraction or New York Heart Association class.</p><p><strong>Conclusions: </strong>Our study demonstrates that molecular phenomapping can stratify patients with HF into distinct subgroups that go beyond predefined clinical classifications.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004953"},"PeriodicalIF":6.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641943","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":"Importance of Clinical, Laboratory, and Genetic Risk Factors for Incident CAD.","authors":"Romit Bhattacharya, Christopher S Marnell, So Mi Jemma Cho, Aniruddh Patel, Yunfeng Ruan, Satoshi Koyama, Amanda Jowell, Mark Trinder, Sara Haidermota, Kim Lannery, Michael C Honigberg, Seyedeh M Zekevat, Ida Surakka, Gina M Peloso, Pradeep Natarajan","doi":"10.1161/CIRCGEN.124.004937","DOIUrl":"10.1161/CIRCGEN.124.004937","url":null,"abstract":"<p><strong>Background: </strong>Prior work suggests modifiable cardiovascular risk factors (CRFs) account for 80% to 90% of the risk for incident myocardial infarction. The contributions of genetic and other novel CRFs have not been simultaneously assessed in contemporary data sets.</p><p><strong>Methods: </strong>In the United Kingdom Biobank, CRFs were identified and Cox proportional hazards models with traditional CRFs (hypertension, diabetes, dyslipidemia, waist-to-hip ratio, diet, exercise, alcohol, and socioeconomic deprivation) and contemporary/genetic CRFs (Lp(a) [lipoprotein(a)], hsCRP [high-sensitivity C-reactive protein], familial hypercholesterolemia variants, and polygenic risk score for coronary artery disease) were constructed for coronary artery disease. Coronary artery disease was defined as a first-time myocardial infarction diagnosis or coronary revascularization. R² was calculated for each model, and the percent contribution of each individual CRF was calculated by the R² percent decrease after its removal.</p><p><strong>Results: </strong>Among 299 707 individuals, the mean (SD) age was 56.2 (8.1) years, and 166 533 (55.6%) were women. Over a median (interquartile range) follow-up of 11.0 (9.6-12.5) years, 17 409 (5.8%) of participants developed myocardial infarction. R² increased from the base model (R², 0.021 [0.020-0.022]), to the clinical model (R², 0.045 [0.043-0.046]), to the contemporary/genetic model (R², 0.053 [0.052-0.055]). The most powerful individual CRFs were hypertension (R² loss, 15.2% [14.5-17.1]) and polygenic risk score for coronary artery disease (R² loss, 12.4% [10.8-13.3]), followed by dyslipidemia (R² loss, 3.4% [2.6-3.5]), diabetes (R² loss, 2.2% [1.5-2.0]), hsCRP (R² loss, 1.8% [1.5-2.0]), and Lp(a) (R² loss, 1.5% [1.2-1.8]).</p><p><strong>Conclusions: </strong>Novel CRFs like polygenic risk score for coronary artery disease, hsCRP, and Lp(a) have similar importance, comparable to traditional CRFs such as hypertension, dyslipidemia, and diabetes, for incident myocardial infarction, highlighting important identifiable residual risk factors.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004937"},"PeriodicalIF":6.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552497","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":"Implementing Precision Medicine for Dilated Cardiomyopathy: Insights From the DCM Consortium.","authors":"Elizabeth Jordan, Hanyu Ni, Patricia Parker, Daniel D Kinnamon, Anjali Owens, Brian Lowes, Chetan Shenoy, Cindy M Martin, Daniel P Judge, Daniel P Fishbein, Douglas Stoller, Elina Minami, Evan P Kransdorf, Frank Smart, Garrie J Haas, Gordon S Huggins, Gregory A Ewald, Jamie Diamond, Jane E Wilcox, Javier Jimenez, Jessica Wang, Jose Tallaj, Mark H Drazner, Mark Hofmeyer, Matthew T Wheeler, Omar Wever Pinzon, Palak Shah, Stephen S Gottlieb, Stuart Katz, Supriya Shore, W H Wilson Tang, Ray E Hershberger","doi":"10.1161/CIRCGEN.125.005078","DOIUrl":"10.1161/CIRCGEN.125.005078","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005078"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316023","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":"Machine Learning-Based Plasma Protein Risk Score Improves Atrial Fibrillation Prediction Over Clinical and Genomic Models.","authors":"Min Seo Kim, Shaan Khurshid, Shinwan Kany, Lu-Chen Weng, Sarah Urbut, Carolina Roselli, Leonoor Wijdeveld, Sean J Jurgens, Joel T Rämö, Patrick T Ellinor, Akl C Fahed","doi":"10.1161/CIRCGEN.124.004943","DOIUrl":"10.1161/CIRCGEN.124.004943","url":null,"abstract":"<p><strong>Background: </strong>Clinical factors discriminate incident atrial fibrillation (AF) risk with moderate accuracy, with only modest improvement after incorporation of polygenic risk scores. Whether emerging large-scale proteomic profiling can augment AF risk estimation is unknown.</p><p><strong>Methods: </strong>In the UK Biobank cohort, we derived and validated a machine learning model to predict incident AF risk using serum proteins (Pro-AF). We compared Pro-AF to a validated clinical risk score (Cohorts for Aging and Genomic Epidemiology-Atrial Fibrillation) and an AF polygenic risk score. Models were evaluated in a multiply resampled test set from nested cross-validation (internal test set), and a sample of UK Biobank participants separate from model development (hold-out test set). Metrics included discrimination of 5-year incident AF using time-dependent area under the receiver operating characteristic curve and net reclassification.</p><p><strong>Results: </strong>Trained in 32 631 UK Biobank participants, Pro-AF predicts incident AF using 121 protein levels (out of 2911 protein analytes). When assessed in the internal test set comprising 30 632 individuals (mean age 57±8 years, 54% women, 2045 AF events) and hold-out test set comprising 13 998 individuals (mean age 57±8 years, 54% women, 870 AF events), discrimination of 5-year incident AF was highest using Pro-AF (area under the receiver operating characteristic curve internal: 0.761 [95% CI, 0.745-0.780], hold-out: 0.763 [0.734-0.784]), followed by Cohorts for Aging and Genomic Epidemiology-Atrial Fibrillation (0.719 [0.700-0.737]; 0.702 [0.668-0.730]) and the polygenic risk score (0.686 [0.668-0.702]; 0.682 [0.660-0.710]). AF risk estimates were well-calibrated, and the addition of Pro-AF led to substantial continuous net reclassification improvement over Cohorts for Aging and Genomic Epidemiology-Atrial Fibrillation (eg, internal test set 0.410 [0.330-0.492]). A simplified Pro-AF including only the 5 most influential proteins (NT-proBNP, EDA2R [ectodysplasin A2 receptor], NPPB [B-type natriuretic peptide], BCAN [brevican core protein], and GDF15 [growth/differentiation factor 15]), retained favorable discriminative value (area under the receiver operating characteristic curve internal: 0.750 [0.733-0.768]; hold-out: 0.759 [0.732-0.790]).</p><p><strong>Conclusions: </strong>A machine learning-based protein score discriminates 5-year incident AF risk favorably compared with clinical and genetic risk factors. Large-scale proteomic analysis may assist in the prioritization of individuals at risk for AF for screening and related preventive interventions.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004943"},"PeriodicalIF":6.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309596","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":"Plasma Proteomics Reveals Dysregulated Pathways Across the Spectrum <i>LMNA</i> Cardiomyopathy.","authors":"Usman A Tahir, Daniel Reichart, Anisha Purohit, Jacob L Barber, Gaurav Tiwari, Laurie Farrell, Julia Marine, Darius Roy, Joshen Patel, Catherine Ireland, Carolyn Y Ho, Christine E Seidman, Robert E Gerszten, Neal K Lakdawala","doi":"10.1161/CIRCGEN.124.004924","DOIUrl":"https://doi.org/10.1161/CIRCGEN.124.004924","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in the <i>lamin A/C</i> (<i>LMNA</i>) gene cause an aggressive form of dilated cardiomyopathy (DCM), marked by higher rates of advanced conduction disease, malignant ventricular tachyarrhythmias, and advanced heart failure compared with other causes of nonischemic cardiomyopathy. However, the mechanisms that drive the development and progression of <i>LMNA</i> DCM are incompletely understood.</p><p><strong>Methods: </strong>To identify proteins and biological pathways associated with likely pathogenic/pathogenic <i>LMNA</i> variants, we measured ≈3000 plasma proteins using the OLINK platform in a genetic DCM cohort consisting of <i>LMNA</i> (n=41) and sarcomeric (n=18) DCM, along with phenotype-negative individuals from family-based cascade screening (n=55) with (<i>LMNA</i>, n=16; sarcomere, n=12) or without the family variant (genotype negative, n=27).</p><p><strong>Results: </strong>We identified several novel proteins associated with <i>LMNA</i> DCM compared with sarcomeric DCM, including EDA2R (ectodysplasin A2 receptor; per log2 fold change in relative protein abundance, β=3.0; <i>P</i>=4×10^-³) and <i>MYL4</i> (myosin light chain 4; β=2.32; <i>P</i>=5×10^-³). Among the proteins associated with <i>LMNA</i> DCM, 26 showed concordant differential gene expression from single-cell sequencing in cardiomyocytes from myocardial biopsies in advanced <i>LMNA</i> heart failure compared with control hearts (false discovery rate, <5%). We performed principal component analyses on these 26 proteins to identify proteomic signatures of <i>LMNA</i> DCM and found the first principal component to be associated with left ventricular ejection fraction and complete heart block in the <i>LMNA</i> DCM cohort. Six proteins-EDA2R, MYL4, CRIM1 (cysteine-rich transmembrane BMP regulator 1), TPR (translocated promoter region), FSTL3 (follistatin-like 3), and NFYA (nuclear transcription factor Y)-were associated with <i>LMNA</i> pathogenic variants across phenotype-negative individuals, DCM, and their respective cardiomyocyte RNA expression profiles in advanced heart failure.</p><p><strong>Conclusions: </strong>Proteomic profiling in individuals with likely pathogenic/pathogenic <i>LMNA</i> variants illuminated integral pathways across the spectrum of <i>LMNA</i> DCM. These findings may help advance genotype-driven biomarker discovery and tailored therapeutic development in <i>LMNA</i> DCM.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004924"},"PeriodicalIF":6.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282639","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":"Correction of the Murine Model of Congenital Heart Disease Associated With the <i>Nkx2-5</i> Mutation Using Prime Editing.","authors":"Toshiyuki Ko, Daigo Nishijo, Atsumi Tsuji-Hosokawa, Iku Tsuchiya, Seitaro Nomura, Bo Zhang, Yue Jiang, Kaho Fujimori, Takashi Hiruma, Ryo Abe, Takahiro Jimba, Shunsuke Inoue, Zhehao Dai, Manami Katoh, Mikako Katagiri, Masamichi Ito, Hiroyuki Morita, Shuji Takada, Norihiko Takeda, Akihiro Umezawa, Issei Komuro","doi":"10.1161/CIRCGEN.124.005194","DOIUrl":"https://doi.org/10.1161/CIRCGEN.124.005194","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005194"},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246682","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":"ALPK3 Heterozygous Truncating Variants Cause Late-Onset Hypertrophic Cardiomyopathy With Frequent Apical Involvement and Apical Aneurysm.","authors":"Leora Busse, Emily A Huth, Maria Roselle Abraham, Theodore Abraham, Arun Padmanabhan, Julianne Wojciak, Gabrielle Wright, Rajani Aatre, Rachel Campagna, Erika Jackson, Sarah Kreykes, Kimberly Lane, Lindsey Sawyer, Chelsea Pappas, Matthew Thomas, Rebecca VanDyke, Vasanth Vedantham, Emily J Higgs","doi":"10.1161/CIRCGEN.125.005186","DOIUrl":"10.1161/CIRCGEN.125.005186","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005186"},"PeriodicalIF":6.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224550","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}