Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers
Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations o...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/8/1424 |
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| author | Mila Glavaški Lazar Velicki Nataša Vučinić |
| author_facet | Mila Glavaški Lazar Velicki Nataša Vučinić |
| author_sort | Mila Glavaški |
| collection | DOAJ |
| description | Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype–phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes. |
| first_indexed | 2024-03-10T23:45:11Z |
| format | Article |
| id | doaj.art-082b0583cb7a46bda2048c6347205d20 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-10T23:45:11Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-082b0583cb7a46bda2048c6347205d202023-11-19T02:06:03ZengMDPI AGMedicina1010-660X1648-91442023-08-01598142410.3390/medicina59081424Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their ModifiersMila Glavaški0Lazar Velicki1Nataša Vučinić2Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, SerbiaFaculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, SerbiaFaculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, SerbiaHypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype–phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes.https://www.mdpi.com/1648-9144/59/8/1424hypertrophic cardiomyopathygeneticsoutcomesgenotypephenotypemodifier |
| spellingShingle | Mila Glavaški Lazar Velicki Nataša Vučinić Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers Medicina hypertrophic cardiomyopathy genetics outcomes genotype phenotype modifier |
| title | Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers |
| title_full | Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers |
| title_fullStr | Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers |
| title_full_unstemmed | Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers |
| title_short | Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers |
| title_sort | hypertrophic cardiomyopathy genetic foundations outcomes interconnections and their modifiers |
| topic | hypertrophic cardiomyopathy genetics outcomes genotype phenotype modifier |
| url | https://www.mdpi.com/1648-9144/59/8/1424 |
| work_keys_str_mv | AT milaglavaski hypertrophiccardiomyopathygeneticfoundationsoutcomesinterconnectionsandtheirmodifiers AT lazarvelicki hypertrophiccardiomyopathygeneticfoundationsoutcomesinterconnectionsandtheirmodifiers AT natasavucinic hypertrophiccardiomyopathygeneticfoundationsoutcomesinterconnectionsandtheirmodifiers |