Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review
Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of ca...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/11/2/41 |
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| author | Andreea Sorina Afana Laura Vasiliu Radu Sascău Robert Daniel Adam Cristina Rădulescu Sebastian Onciul Eliza Cinteză Adela Chirita-Emandi Ruxandra Jurcuț |
| author_facet | Andreea Sorina Afana Laura Vasiliu Radu Sascău Robert Daniel Adam Cristina Rădulescu Sebastian Onciul Eliza Cinteză Adela Chirita-Emandi Ruxandra Jurcuț |
| author_sort | Andreea Sorina Afana |
| collection | DOAJ |
| description | Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the <i>PLN</i> p.Leu39* variant. A cohort including 11 <i>PLN</i> patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. <i>PLN</i> p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (<i>MYBPC3/MYH7</i>). Overall, the clinical characteristics and examination findings of patients carrying <i>PLN</i> p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in <i>PLN</i> patients than in those with <i>MYBPC3/MYH7</i>-related diseases. |
| first_indexed | 2024-03-07T22:27:44Z |
| format | Article |
| id | doaj.art-829d05c4bd95452eb96d714d3fc7674b |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-07T22:27:44Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-829d05c4bd95452eb96d714d3fc7674b2024-02-23T15:21:42ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252024-01-011124110.3390/jcdd11020041Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature ReviewAndreea Sorina Afana0Laura Vasiliu1Radu Sascău2Robert Daniel Adam3Cristina Rădulescu4Sebastian Onciul5Eliza Cinteză6Adela Chirita-Emandi7Ruxandra Jurcuț8Expert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, RomaniaInstitute of Cardiovascular Diseases “Prof. Dr. George I.M. Georgescu”, 700503 Iași, RomaniaInstitute of Cardiovascular Diseases “Prof. Dr. George I.M. Georgescu”, 700503 Iași, RomaniaExpert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, RomaniaCardiology Department, University of Medicine and Pharmacy “Carol Davila”, 8 Eroii Sanitari Blvd., 050474 Bucharest, RomaniaCardiology Department, University of Medicine and Pharmacy “Carol Davila”, 8 Eroii Sanitari Blvd., 050474 Bucharest, RomaniaCardiology Department, University of Medicine and Pharmacy “Carol Davila”, 8 Eroii Sanitari Blvd., 050474 Bucharest, RomaniaDepartment of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babeș” Timișoara, 2 Piaţa Eftimie Murgu Street, 300041 Timişoara, RomaniaExpert Center for Genetic Cardiovascular Diseases, Emergency Institute for Cardiovascular Diseases, 258 Fundeni Street, 022328 Bucharest, RomaniaHypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the <i>PLN</i> p.Leu39* variant. A cohort including 11 <i>PLN</i> patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. <i>PLN</i> p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (<i>MYBPC3/MYH7</i>). Overall, the clinical characteristics and examination findings of patients carrying <i>PLN</i> p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in <i>PLN</i> patients than in those with <i>MYBPC3/MYH7</i>-related diseases.https://www.mdpi.com/2308-3425/11/2/41phospholambanhypertrophic cardiomyopathygenetic testing |
| spellingShingle | Andreea Sorina Afana Laura Vasiliu Radu Sascău Robert Daniel Adam Cristina Rădulescu Sebastian Onciul Eliza Cinteză Adela Chirita-Emandi Ruxandra Jurcuț Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review Journal of Cardiovascular Development and Disease phospholamban hypertrophic cardiomyopathy genetic testing |
| title | Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review |
| title_full | Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review |
| title_fullStr | Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review |
| title_full_unstemmed | Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review |
| title_short | Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review |
| title_sort | phospholamban p leu39 cardiomyopathy compared with other sarcomeric cardiomyopathies age matched patient cohorts and literature review |
| topic | phospholamban hypertrophic cardiomyopathy genetic testing |
| url | https://www.mdpi.com/2308-3425/11/2/41 |
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