دورية أكاديمية
Cadherin 2-Related Arrhythmogenic Cardiomyopathy: Prevalence and Clinical Features
| العنوان: | Cadherin 2-Related Arrhythmogenic Cardiomyopathy: Prevalence and Clinical Features |
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| المؤلفون: | Ghidoni A., Elliott P. M., Syrris P., Calkins H., James C. A., Judge D. P., Murray B., Barc J., Probst V., Schott J. J., Song J. -P., Hauer R. N. W., Hoorntje E. T., Van Tintelen J. P., Schulze-Bahr E., Hamilton R. M., Mittal K., Semsarian C., Behr E. R., Ackerman M. J., Basso C., Parati G., Gentilini D., Kotta M. -C., Mayosi B. M., Schwartz P. J., Crotti L. |
| المساهمون: | Ghidoni, A, Elliott, P, Syrris, P, Calkins, H, James, C, Judge, D, Murray, B, Barc, J, Probst, V, Schott, J, Song, J, Hauer, R, Hoorntje, E, Van Tintelen, J, Schulze-Bahr, E, Hamilton, R, Mittal, K, Semsarian, C, Behr, E, Ackerman, M, Basso, C, Parati, G, Gentilini, D, Kotta, M, Mayosi, B, Schwartz, P, Crotti, L |
| بيانات النشر: | Lippincott Williams and Wilkins US |
| سنة النشر: | 2021 |
| المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| مصطلحات موضوعية: | cadherin, cardiomyopathy, mutation, sudden cardiac death, tachycardia |
| الوصف: | Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by fibrofatty replacement of the right and left ventricle, often causing ventricular dysfunction and life-threatening arrhythmias. Variants in desmosomal genes account for up to 60% of cases. Our objective was to establish the prevalence and clinical features of ACM stemming from pathogenic variants in the nondesmosomal cadherin 2 (CDH2), a novel genetic substrate of ACM. Methods: A cohort of 500 unrelated patients with a definite diagnosis of ACM and no disease-causing variants in the main ACM genes was assembled. Genetic screening of CDH2 was performed through next-generation or Sanger sequencing. Whenever possible, cascade screening was initiated in the families of CDH2-positive probands, and clinical evaluation was performed. Results: Genetic screening of CDH2 led to the identification of 7 rare variants: 5, identified in 6 probands, were classified as pathogenic or likely pathogenic. The previously established p.D407N pathogenic variant was detected in 2 additional probands. Probands and family members with pathogenic/likely pathogenic variants in CDH2 were clinically evaluated, and along with previously published cases, altogether contributed to the identification of gene-specific features (13 cases from this cohort and 11 previously published, for a total of 9 probands and 15 family members). Ventricular arrhythmic events occurred in most CDH2-positive subjects (20/24, 83%), while the occurrence of heart failure was rare (2/24, 8.3%). Among probands, sustained ventricular tachycardia and sudden cardiac death occurred in 5/9 (56%). Conclusions: In this worldwide cohort of previously genotype-negative ACM patients, the prevalence of probands with CDH2 pathogenic/likely pathogenic variants was 1.2% (6/500). Our data show that this cohort of CDH2-ACM patients has a high incidence of ventricular arrhythmias, while evolution toward heart failure is rare. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33566628; info:eu-repo/semantics/altIdentifier/wos/WOS:000641550000005; volume:14; issue:2; firstpage:159; lastpage:169; numberofpages:11; journal:CIRCULATION; http://hdl.handle.net/10281/354087Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85104674276 |
| DOI: | 10.1161/CIRCGEN.120.003097 |
| الإتاحة: | https://doi.org/10.1161/CIRCGEN.120.003097Test http://hdl.handle.net/10281/354087Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.DF71E7DD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/CIRCGEN.120.003097 |
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