Analyzing the Genetic Causes of Pediatric Inherited Cardiomyopathy in Middle Eastern Patients
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction:
Introduction: Pediatric cardiomyopathy (piCMP) is a diverse group of heart muscle disorders in children that can lead to heart failure, arrhythmias, or sudden cardiac arrest. Its genetics often involve mutations in various genes related to cardiac structure and function, highlighting the importance of comprehensive genetic screening to identify underlying causes and inform treatment strategies. We have analyzed the genomes of piCMP patients in the less-studied Middle Eastern population.
Methods:
Methods: Genome sequencing was conducted on 15 unrelated families with piCMP-affected offspring. A comprehensive cardiomyopathy panel comprising 177 candidate genes was created, and each identified variant was assessed according to the ACMG guidelines and analyzed using the gnomAD, ClinVar, UCSC, and other databases.
Results:
Results: Among the 94 detected rare variants, we classified 4 novel variants (ANK2 c.7594G>A, NEXN c.1318dup, MYL2 c.259G>T, FHOD3 c.3065_3066insA) as likely pathogenic, while 4 were previously classified as pathogenic based on ClinVar (MYH7 c.1357C>T and c.5401G>A, SLC22A5 c.505C>T, GAA c.2734del). Additionally, we classified 5 variants in specific genes as VUS with high ACMG scores (4-5).
Conclusion:
Conclusion: The diagnostic recall rate in our cohort was 47%, consistent with previously reported rates in pediatric populations (39-79%). The remaining 52% of unsolved cases present a significant opportunity for the discovery of novel disease genes and variants.
Introduction: Pediatric cardiomyopathy (piCMP) is a diverse group of heart muscle disorders in children that can lead to heart failure, arrhythmias, or sudden cardiac arrest. Its genetics often involve mutations in various genes related to cardiac structure and function, highlighting the importance of comprehensive genetic screening to identify underlying causes and inform treatment strategies. We have analyzed the genomes of piCMP patients in the less-studied Middle Eastern population.
Methods:
Methods: Genome sequencing was conducted on 15 unrelated families with piCMP-affected offspring. A comprehensive cardiomyopathy panel comprising 177 candidate genes was created, and each identified variant was assessed according to the ACMG guidelines and analyzed using the gnomAD, ClinVar, UCSC, and other databases.
Results:
Results: Among the 94 detected rare variants, we classified 4 novel variants (ANK2 c.7594G>A, NEXN c.1318dup, MYL2 c.259G>T, FHOD3 c.3065_3066insA) as likely pathogenic, while 4 were previously classified as pathogenic based on ClinVar (MYH7 c.1357C>T and c.5401G>A, SLC22A5 c.505C>T, GAA c.2734del). Additionally, we classified 5 variants in specific genes as VUS with high ACMG scores (4-5).
Conclusion:
Conclusion: The diagnostic recall rate in our cohort was 47%, consistent with previously reported rates in pediatric populations (39-79%). The remaining 52% of unsolved cases present a significant opportunity for the discovery of novel disease genes and variants.