Cardiogenetics最新文献

Gene-Specific Discriminative Echocardiogram Findings in Hypertrophic Cardiomyopathy Determined Using Artificial Intelligence: A Pilot Study 利用人工智能确定肥厚型心肌病的基因特异性超声心动图结果：试点研究

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Cardiogenetics Pub Date : 2023-12-25 DOI: 10.3390/cardiogenetics14010001

Milan Glavaški, Aleksandra Ilić, L. Velicki

{"title":"Gene-Specific Discriminative Echocardiogram Findings in Hypertrophic Cardiomyopathy Determined Using Artificial Intelligence: A Pilot Study","authors":"Milan Glavaški, Aleksandra Ilić, L. Velicki","doi":"10.3390/cardiogenetics14010001","DOIUrl":"https://doi.org/10.3390/cardiogenetics14010001","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is among the most common forms of cardiomyopathies, with a prevalence of 1:200 to 1:500 people. HCM is caused by variants in genes encoding cardiac sarcomeric proteins, of which a majority reside in MYH7, MYBPC3, and TNNT2. Up to 40% of the HCM cases do not have any known HCM variant. Genotype–phenotype associations in HCM remain incompletely understood. This study involved two visits of 46 adult patients with a confirmed diagnosis of HCM. In total, 174 genes were analyzed on the Next-Generation Sequencing platform, and transthoracic echocardiography was performed. Gene-specific discriminative echocardiogram findings were identified using the computer vision library Fast AI. This was accomplished with the generation of deep learning models for the classification of ultrasonic images based on the underlying genotype and a later analysis of the most decisive image regions. Gene-specific echocardiogram findings were identified: for variants in the MYH7 gene (vs. variant not detected), the most discriminative structures were the septum, left ventricular outflow tract (LVOT) segment, anterior wall, apex, right ventricle, and mitral apparatus; for variants in MYBPC3 gene (vs. variant not detected) these were the septum, left ventricle, and left ventricle/chamber; while for variants in the TNNT2 gene (vs. variant not detected), the most discriminative structures were the septum and right ventricle.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"57 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139159616","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}

引用次数: 0

Inherited Arrhythmogenic Syndromes 遗传性致心律失常综合征

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Cardiogenetics Pub Date : 2023-12-04 DOI: 10.3390/cardiogenetics13040016

G. Sarquella-Brugada, Ó. Campuzano

引用次数: 0

From Natural History to Contemporary Management of Aortic Diseases: A State-of-the-Art Review of Thoracic Aortic Aneurysm 从主动脉疾病的自然史到当代管理：胸主动脉瘤最新进展回顾

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Cardiogenetics Pub Date : 2023-11-29 DOI: 10.3390/cardiogenetics13040015

Yuliya Paulenka, Christopher Lee, Mays Tawayha, Sam Dow, Kajal Shah, Stanislav Henkin, Wassim Mosleh

引用次数: 0

Sudden Cardiac Death in Biventricular Arrhythmogenic Cardiomyopathy: A New Undescribed Variant of the MYH6 Gene 双室性心律失常性心肌病的心源性猝死:MYH6基因的一种新的未描述变体

Cardiogenetics Pub Date : 2023-10-23 DOI: 10.3390/cardiogenetics13040014

Pedro Garcia Brás, Isabel Cardoso, José Viegas, Diana Antunes, Sílvia Aguiar Rosa

{"title":"Sudden Cardiac Death in Biventricular Arrhythmogenic Cardiomyopathy: A New Undescribed Variant of the MYH6 Gene","authors":"Pedro Garcia Brás, Isabel Cardoso, José Viegas, Diana Antunes, Sílvia Aguiar Rosa","doi":"10.3390/cardiogenetics13040014","DOIUrl":"https://doi.org/10.3390/cardiogenetics13040014","url":null,"abstract":"Arrhythmogenic cardiomyopathy (ACM) may present with sudden cardiac arrest (SCA), and demonstration of a pathogenic variant in ACM-related genes is crucial for its definitive diagnosis. A 42-year-old female patient with family history of sudden cardiac death (SCD) was referred to the cardiomyopathy clinic after two episodes of aborted SCA. In the second episode, the patient was transported under cardiopulmonary resuscitation (downtime of 57 min) until extracorporeal membrane oxygenation was implanted. A thorough diagnostic work-up led to a diagnosis of biventricular ACM. Genetic testing revealed a previously undescribed variant in ACM patients in the MYH6 gene, c.3673G>T p.(Glu 1225*), which inserts a premature stop codon. This was considered a possible pathogenic variant originating a truncated protein, previously undescribed in ACM. The patient’s 23-year-old daughter was positive for the MYH6 variant and had ECG abnormalities suggestive of ACM. This case details the complex differential diagnosis of SCA and explores the current recommendations for the diagnosis of biventricular ACM. The identification of a MYH6 variant in a patient with ACM, recurrent SCA, and family history of SCD appears to support the hypothesis of the pathogenicity of MYH6 variants in ACM, in which the association of phenotype with sarcomere variants is still unclear.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"16 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135405807","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}

引用次数: 0

A Family with a Single LMNA Mutation Illustrates Diversity in Cardiac Phenotypes Associated with Laminopathic Progeroid Syndromes 一个具有单一LMNA突变的家族说明了与层状病类早衰综合征相关的心脏表型多样性

Cardiogenetics Pub Date : 2023-09-26 DOI: 10.3390/cardiogenetics13040013

Anna-Gaëlle Giguet-Valard, Astrid Monfort, Hugues Lucron, Helena Mosbah, Franck Boccara, Camille Vatier, Corinne Vigouroux, Pascale Richard, Karim Wahbi, Remi Bellance, Elisabeth Sarrazin, Jocelyn Inamo

{"title":"A Family with a Single LMNA Mutation Illustrates Diversity in Cardiac Phenotypes Associated with Laminopathic Progeroid Syndromes","authors":"Anna-Gaëlle Giguet-Valard, Astrid Monfort, Hugues Lucron, Helena Mosbah, Franck Boccara, Camille Vatier, Corinne Vigouroux, Pascale Richard, Karim Wahbi, Remi Bellance, Elisabeth Sarrazin, Jocelyn Inamo","doi":"10.3390/cardiogenetics13040013","DOIUrl":"https://doi.org/10.3390/cardiogenetics13040013","url":null,"abstract":"The likely pathogenic variant c.407A>T p.Asp136Val of the LMNA gene has been recently described in a young woman presenting with atypical progeroid syndrome, associated with severe aortic valve stenosis. We further describe the cardiovascular involvement associated with the syndrome in her family. We identified seven members with a general presentation suggestive of progeroid syndrome. All of them presented heart conduction abnormalities: degenerative cardiac diseases such as coronary artery disease (two subjects) and aortic stenosis (three subjects) occurred in the 3rd–5th decade, and a young patient developed a severe dilated cardiomyopathy, leading to death at 15 years of age. The likely pathogenic variant was found in all the patients who consented to carry out the genetic test. This diverse family cardiologic phenotype emphasizes the complex molecular background at play in lamin-involved cardiac diseases, and the need for early and thorough cardiac evaluations in patients with laminopathic progeroid syndromes.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135719366","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}

引用次数: 0

Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia HCN4中与窦性心动过缓相关的A414G功能缺失突变的功能特征

IF 0.6

Cardiogenetics Pub Date : 2023-08-04 DOI: 10.3390/cardiogenetics13030012

A. Verkerk, R. Wilders

{"title":"Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia","authors":"A. Verkerk, R. Wilders","doi":"10.3390/cardiogenetics13030012","DOIUrl":"https://doi.org/10.3390/cardiogenetics13030012","url":null,"abstract":"Patients carrying the heterozygous A414G mutation in the HCN4 gene, which encodes the HCN4 protein, demonstrate moderate to severe bradycardia of the heart. Tetramers of HCN4 subunits compose the ion channels in the sinus node that carry the hyperpolarization-activated ‘funny’ current (If), also named the ‘pacemaker current’. If plays an essential modulating role in sinus node pacemaker activity. To assess the mechanism by which the A414G mutation results in sinus bradycardia, we first performed voltage clamp measurements on wild-type (WT) and heterozygous mutant HCN4 channels expressed in Chinese hamster ovary (CHO) cells. These experiments were performed at physiological temperature using the amphotericin-perforated patch-clamp technique. Next, we applied the experimentally observed mutation-induced changes in the HCN4 current of the CHO cells to If of the single human sinus node cell model developed by Fabbri and coworkers. The half-maximal activation voltage V1/2 of the heterozygous mutant HCN4 current was 19.9 mV more negative than that of the WT HCN4 current (p < 0.001). In addition, the voltage dependence of the heterozygous mutant HCN4 current (de)activation time constant showed a −11.9 mV shift (p < 0.001) compared to the WT HCN4 current. The fully-activated current density, the slope factor of the activation curve, and the reversal potential were not significantly affected by the heterozygous A414G mutation. In the human sinus node computer model, the cycle length was substantially increased, almost entirely due to the shift in the voltage dependence of steady-state activation, and this increase was more prominent under vagal tone. The introduction of a passive atrial load into the model sinus node cell further reduced the beating rate, demonstrating that the bradycardia of the sinus node was even more pronounced by interactions between the sinus node and atria. In conclusion, the experimentally identified A414G-induced changes in If can explain the clinically observed sinus bradycardia in patients carrying the A414G HCN4 gene mutation.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43339726","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}

引用次数: 0

Unraveling the Genetic and Epigenetic Complexities of Hereditary Aortic Diseases and the Breakthroughs of Precision Medicine: An Editorial 揭示遗传性主动脉疾病的遗传和表观遗传复杂性以及精准医学的突破:社论

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Cardiogenetics Pub Date : 2023-07-18 DOI: 10.3390/cardiogenetics13030011

F. Awa, Mays Tawayha, Wassim Mosleh

引用次数: 0

GMDS Intragenic Deletions Associate with Congenital Heart Disease including Ebstein Anomaly 基因内缺失与先天性心脏病相关，包括Ebstein异常

IF 0.6

Cardiogenetics Pub Date : 2023-07-06 DOI: 10.3390/cardiogenetics13030010

Shirley Lo-A-Njoe, Eline A. Verberne, L. T. van der Veken, Eric Arends, J. van Tintelen, A. Postma, M. V. van Haelst

{"title":"GMDS Intragenic Deletions Associate with Congenital Heart Disease including Ebstein Anomaly","authors":"Shirley Lo-A-Njoe, Eline A. Verberne, L. T. van der Veken, Eric Arends, J. van Tintelen, A. Postma, M. V. van Haelst","doi":"10.3390/cardiogenetics13030010","DOIUrl":"https://doi.org/10.3390/cardiogenetics13030010","url":null,"abstract":"Ebstein anomaly is a rare heterogeneous congenital heart defect (CHD) with a largely unknown etiology. We present a 6-year-old girl with Ebstein anomaly, atrial septum defect, hypoplastic right ventricle, and persistent left superior vena cava who has a de novo intragenic ~403 kb deletion of the GDP-mannose 4,6-dehydratase (GMDS) gene. GMDS is located on chromosome 6p25.3 and encodes the rate limiting enzyme in GDP-fucose synthesis, which is used to fucosylate many proteins, including Notch1, which plays a critical role during mammalian cardiac development. The GMDS locus has sporadically been associated with Ebstein anomaly (large deletion) and tetralogy of Fallot (small deletion). Given its function and the association with CHD, we hypothesized that loss-of-function of, or alterations in, GMDS could play a role in the development of Ebstein anomaly. We collected a further 134 cases with Ebstein anomaly and screened them for genomic aberrations of the GMDS locus. No additional GMDS genomic aberrations were identified. In conclusion, we describe a de novo intragenic GMDS deletion associated with Ebstein anomaly. Together with previous reports, this second case suggests that GMDS deletions could be a rare cause for congenital heart disease, in particular Ebstein anomaly.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49160822","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}

引用次数: 0

Sarcomeric versus Non-Sarcomeric HCM 肌性与非肌性HCM

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Cardiogenetics Pub Date : 2023-06-02 DOI: 10.3390/cardiogenetics13020009

F. Borrelli, M. Losi, G. Canciello, G. Todde, E. Perillo, Leopoldo Ordine, G. Frisso, G. Esposito, R. Lombardi

引用次数: 0

Diagnosis and Treatment of Obstructive Hypertrophic Cardiomyopathy 梗阻性肥厚型心肌病的诊断与治疗

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Cardiogenetics Pub Date : 2023-05-15 DOI: 10.3390/cardiogenetics13020008

G. Todde, G. Canciello, F. Borrelli, E. Perillo, G. Esposito, R. Lombardi, M. Losi

引用次数: 1