Pub Date : 2023-12-25DOI: 10.3390/cardiogenetics14010001
Milan Glavaški, Aleksandra Ilić, L. Velicki
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.
{"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}
Pub Date : 2023-12-04DOI: 10.3390/cardiogenetics13040016
G. Sarquella-Brugada, Ó. Campuzano
Inherited arrhythmogenic syndromes (IASs) are a heterogeneous group of rare cardiac entities of genetic origin [...]
遗传性心律失常综合征(ias)是一组罕见的遗传性心脏疾病[…]
{"title":"Inherited Arrhythmogenic Syndromes","authors":"G. Sarquella-Brugada, Ó. Campuzano","doi":"10.3390/cardiogenetics13040016","DOIUrl":"https://doi.org/10.3390/cardiogenetics13040016","url":null,"abstract":"Inherited arrhythmogenic syndromes (IASs) are a heterogeneous group of rare cardiac entities of genetic origin [...]","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"20 6","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138601968","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}
Pub Date : 2023-11-29DOI: 10.3390/cardiogenetics13040015
Yuliya Paulenka, Christopher Lee, Mays Tawayha, Sam Dow, Kajal Shah, Stanislav Henkin, Wassim Mosleh
Thoracic aortic aneurysms (TAAs) are commonly seen in cardiovascular practice. Acquired and genetic conditions contribute to TAA formation. The natural history of genetically mediated TAA underscores the importance of early detection, regular monitoring, and prompt treatment to prevent complications, including dissection or rupture. The prognosis is poor in the event of acute dissection, with high rates of in-hospital mortality. Healthcare providers need to remain vigilant in their efforts to identify and surveil TAA to reduce the risk of complications. In this manuscript, we review the natural history of TAA, discuss the most common causes leading to the development of TAA, assess the value and limitations of diagnostic modalities, and review the management and long-term surveillance of patients with aortic disease.
{"title":"From Natural History to Contemporary Management of Aortic Diseases: A State-of-the-Art Review of Thoracic Aortic Aneurysm","authors":"Yuliya Paulenka, Christopher Lee, Mays Tawayha, Sam Dow, Kajal Shah, Stanislav Henkin, Wassim Mosleh","doi":"10.3390/cardiogenetics13040015","DOIUrl":"https://doi.org/10.3390/cardiogenetics13040015","url":null,"abstract":"Thoracic aortic aneurysms (TAAs) are commonly seen in cardiovascular practice. Acquired and genetic conditions contribute to TAA formation. The natural history of genetically mediated TAA underscores the importance of early detection, regular monitoring, and prompt treatment to prevent complications, including dissection or rupture. The prognosis is poor in the event of acute dissection, with high rates of in-hospital mortality. Healthcare providers need to remain vigilant in their efforts to identify and surveil TAA to reduce the risk of complications. In this manuscript, we review the natural history of TAA, discuss the most common causes leading to the development of TAA, assess the value and limitations of diagnostic modalities, and review the management and long-term surveillance of patients with aortic disease.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"12 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139211282","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}
Pub Date : 2023-10-23DOI: 10.3390/cardiogenetics13040014
Pedro Garcia Brás, Isabel Cardoso, José Viegas, Diana Antunes, Sílvia Aguiar Rosa
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.
{"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}
Pub Date : 2023-09-26DOI: 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
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.
{"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}
Pub Date : 2023-08-04DOI: 10.3390/cardiogenetics13030012
A. Verkerk, R. Wilders
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.
{"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}
Pub Date : 2023-07-18DOI: 10.3390/cardiogenetics13030011
F. Awa, Mays Tawayha, Wassim Mosleh
The field of genetics in cardiovascular disease has introduced new possibilities for understanding the fundamental causes of aortic diseases [...]
心血管疾病遗传学领域为理解主动脉疾病的根本原因提供了新的可能性[…]
{"title":"Unraveling the Genetic and Epigenetic Complexities of Hereditary Aortic Diseases and the Breakthroughs of Precision Medicine: An Editorial","authors":"F. Awa, Mays Tawayha, Wassim Mosleh","doi":"10.3390/cardiogenetics13030011","DOIUrl":"https://doi.org/10.3390/cardiogenetics13030011","url":null,"abstract":"The field of genetics in cardiovascular disease has introduced new possibilities for understanding the fundamental causes of aortic diseases [...]","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49126033","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}
Pub Date : 2023-07-06DOI: 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
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.
{"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}
Pub Date : 2023-06-02DOI: 10.3390/cardiogenetics13020009
F. Borrelli, M. Losi, G. Canciello, G. Todde, E. Perillo, Leopoldo Ordine, G. Frisso, G. Esposito, R. Lombardi
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disorder and is characterized by left ventricular hypertrophy (LVH), which is unexplained by abnormal loading conditions. HCM is inherited as an autosomal dominant trait and, in about 40% of patients, the causal mutation is identified in genes encoding sarcomere proteins. According to the results of genetic screening, HCM patients are currently categorized in two main sub-populations: sarcomeric-positive (Sarc+) patients, in whom the causal mutation is identified in a sarcomeric gene; and sarcomeric-negative (Sarc−) patients, in whom a causal mutation has not been identified. In rare cases, Sarc− HCM cases may be caused by pathogenic variants in non-sarcomeric genes. The aim of this review is to describe the differences in the phenotypic expression and clinical outcomes of Sarc+ and Sarc− HCM and to briefly discuss the current knowledge about HCM caused by rare non-sarcomeric mutations.
{"title":"Sarcomeric versus Non-Sarcomeric HCM","authors":"F. Borrelli, M. Losi, G. Canciello, G. Todde, E. Perillo, Leopoldo Ordine, G. Frisso, G. Esposito, R. Lombardi","doi":"10.3390/cardiogenetics13020009","DOIUrl":"https://doi.org/10.3390/cardiogenetics13020009","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disorder and is characterized by left ventricular hypertrophy (LVH), which is unexplained by abnormal loading conditions. HCM is inherited as an autosomal dominant trait and, in about 40% of patients, the causal mutation is identified in genes encoding sarcomere proteins. According to the results of genetic screening, HCM patients are currently categorized in two main sub-populations: sarcomeric-positive (Sarc+) patients, in whom the causal mutation is identified in a sarcomeric gene; and sarcomeric-negative (Sarc−) patients, in whom a causal mutation has not been identified. In rare cases, Sarc− HCM cases may be caused by pathogenic variants in non-sarcomeric genes. The aim of this review is to describe the differences in the phenotypic expression and clinical outcomes of Sarc+ and Sarc− HCM and to briefly discuss the current knowledge about HCM caused by rare non-sarcomeric mutations.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41490003","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}
Pub Date : 2023-05-15DOI: 10.3390/cardiogenetics13020008
G. Todde, G. Canciello, F. Borrelli, E. Perillo, G. Esposito, R. Lombardi, M. Losi
Left ventricular outflow obstruction (LVOTO) and diastolic dysfunction are the main pathophysiological characteristics of hypertrophic cardiomyopathy (HCM)LVOTO, may be identified in more than half of HCM patients and represents an important determinant of symptoms and a predictor of worse prognosis. This review aims to clarify the LVOTO mechanism in, diagnosis of, and therapeutic strategies for patients with obstructive HCM.
{"title":"Diagnosis and Treatment of Obstructive Hypertrophic Cardiomyopathy","authors":"G. Todde, G. Canciello, F. Borrelli, E. Perillo, G. Esposito, R. Lombardi, M. Losi","doi":"10.3390/cardiogenetics13020008","DOIUrl":"https://doi.org/10.3390/cardiogenetics13020008","url":null,"abstract":"Left ventricular outflow obstruction (LVOTO) and diastolic dysfunction are the main pathophysiological characteristics of hypertrophic cardiomyopathy (HCM)LVOTO, may be identified in more than half of HCM patients and represents an important determinant of symptoms and a predictor of worse prognosis. This review aims to clarify the LVOTO mechanism in, diagnosis of, and therapeutic strategies for patients with obstructive HCM.","PeriodicalId":41330,"journal":{"name":"Cardiogenetics","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49299547","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}
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