Scholarlink

Background <p>Cardiomyopathies (CMs) present phenotypically on a spectrum and in a proportion of patients the initial presentation is sudden cardiac arrest (SCA). Studies performing genetic screening of SCA survivors have identified (likely) pathogenic (LP/P) variants in 2–50% of probands, with mean cohort ages ranging from 28 to 64&#xa0;years. Due to inconsistent data in the literature, our study aimed to genetically characterise Slovenian SCA survivors with clinically confirmed/suspected cardiomyopathy (CM). The present study included 29 probands (17 women, 59%) with clinically confirmed/suspected CM who survived SCA and were referred to the Clinical Institute of Genomic Medicine for genetic testing between January 2010 and July 2024. The majority of probands (23; 79%) underwent whole exome sequencing, and the remainder either clinical exome (5; 17%) or panel sequencing (1; 4%). Genetic data were analysed following ACMG/AMP guidelines and ACGS recommendations.</p> Results <p>Probands survived SCA at a mean age of 49 ± 17&#xa0;years (range 15–71), and 12 (41%) were &lt; 50&#xa0;years old. The majority had clinically confirmed/suspected arrhythmogenic (10; 34.5%) or dilated (9; 31.0%) CM, while the remainder had clinically undefined (5; 17.2%), hypertrophic (4; 13.8%), or non-compaction (1; 3.4%) CM.</p> <p>Seven LP/P variants in CM-related genes were identified in eight (28.6%) probands. In addition, 16 variants of uncertain significance (VUS) were identified in 12 (41.3%) probands.</p> <p>Probands’ age at SCA did not significantly affect the yield, as LP/P variants were identified in four probands &lt; 50&#xa0;years at SCA and in four &gt; 50&#xa0;years (<i>p</i> = 0.56), nor did the positive family history of heart disease (<i>p</i> = 0.55) or sudden cardiac death (<i>p</i> = 0.43).</p> <p>There were also no significant differences in probands' age and test outcome, as the mean age of patients with LP/P variants was 46 ± 21&#xa0;years, those with the VUS(s) were 45 ± 15&#xa0;years, and those without candidate variant(s) were 55 ± 12&#xa0;years (<i>p</i> = 0.41).</p> Conclusions <p>LP/P variants were identified in almost one-third of Slovenian SCA survivors with clinically confirmed/suspected CM. Genetic testing of SCA survivors with structural clinical findings provides additional confirmation of the clinical diagnosis and a basis for identifying relatives at risk of heart disease, allowing for better management.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Spectrum of genetic variants and yield of genetic testing in Slovenian probands with suspected cardiomyopathies surviving sudden cardiac arrest

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月18日

查看全文
  • Nina Vodnjov,
  • Aleš Maver,
  • Borut Petelin,
  • Karin Writzl

摘要

Background

Cardiomyopathies (CMs) present phenotypically on a spectrum and in a proportion of patients the initial presentation is sudden cardiac arrest (SCA). Studies performing genetic screening of SCA survivors have identified (likely) pathogenic (LP/P) variants in 2–50% of probands, with mean cohort ages ranging from 28 to 64 years. Due to inconsistent data in the literature, our study aimed to genetically characterise Slovenian SCA survivors with clinically confirmed/suspected cardiomyopathy (CM). The present study included 29 probands (17 women, 59%) with clinically confirmed/suspected CM who survived SCA and were referred to the Clinical Institute of Genomic Medicine for genetic testing between January 2010 and July 2024. The majority of probands (23; 79%) underwent whole exome sequencing, and the remainder either clinical exome (5; 17%) or panel sequencing (1; 4%). Genetic data were analysed following ACMG/AMP guidelines and ACGS recommendations.

Results

Probands survived SCA at a mean age of 49 ± 17 years (range 15–71), and 12 (41%) were < 50 years old. The majority had clinically confirmed/suspected arrhythmogenic (10; 34.5%) or dilated (9; 31.0%) CM, while the remainder had clinically undefined (5; 17.2%), hypertrophic (4; 13.8%), or non-compaction (1; 3.4%) CM.

Seven LP/P variants in CM-related genes were identified in eight (28.6%) probands. In addition, 16 variants of uncertain significance (VUS) were identified in 12 (41.3%) probands.

Probands’ age at SCA did not significantly affect the yield, as LP/P variants were identified in four probands < 50 years at SCA and in four > 50 years (p = 0.56), nor did the positive family history of heart disease (p = 0.55) or sudden cardiac death (p = 0.43).

There were also no significant differences in probands' age and test outcome, as the mean age of patients with LP/P variants was 46 ± 21 years, those with the VUS(s) were 45 ± 15 years, and those without candidate variant(s) were 55 ± 12 years (p = 0.41).

Conclusions

LP/P variants were identified in almost one-third of Slovenian SCA survivors with clinically confirmed/suspected CM. Genetic testing of SCA survivors with structural clinical findings provides additional confirmation of the clinical diagnosis and a basis for identifying relatives at risk of heart disease, allowing for better management.