Dataset Information
Prevalence and potential genetic determinants of young sudden unexplained death victims with suspected arrhythmogenic mitral valve prolapse syndrome.
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ABSTRACT: Background
Mitral valve prolapse (MVP) is largely considered a benign condition. However, MVP is over-represented consistently in sudden unexplained death in the young (SUDY) cohorts.Objective
To determine the prevalence and potential genetic underpinnings of suspected arrhythmogenic MVP in a referral cohort of SUDY cases.Methods
In this retrospective study, medical records/autopsy reports and whole exome molecular autopsy (WEMA) results for 77 SUDY victims (27 female; average age at death 20.6 ± 8.9 years) were reviewed for evidence of myxomatous MVP and left ventricle (LV) fibrosis. Variants detected in the prespecified 147 WEMA gene panel with a minor allele frequency ≤ 0.001 in public exomes/genomes were classified using the 2015 American College of Medical Genetics (ACMG) guidelines.Results
Overall, 6 of 77 (7.8%; 2 female; average age at death 20.7 ± 6.9 years) SUDY cases had MVP as the lone abnormal postmortem finding. The majority had bileaflet involvement (5/6; 83%) and microscopic LV fibrosis (5/6; 83%). In 2 SUDY cases (33%), subjects were diagnosed with MVP by echocardiography prior to death. Unexpectedly, an ACMG pathogenic/likely pathogenic (P/LP) was more likely to be detected in SUDY cases with MVP than those without (3/6 [50%] vs 9/71 [13%]; P < .05). Interestingly, the 3 variants identified in MVP-positive SUDY cases localized to genes associated previously with a cardiomyopathy/channelopathy predisposition (p.E1518fsX25-DMD, p.S285N-RYR2, and p.R109X-TTN).Conclusion
This WEMA series provides additional evidence that the combination of MVP and LV fibrosis underlies an unexpected number of SUDY cases. Whether P/LP variants in cardiomyopathy/channelopathy-susceptibility genes contribute to the pathogenesis of arrhythmogenic MVP requires further investigation.
SUBMITTER: Giudicessi JR
PROVIDER: S-EPMC8505213 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Prevalence and potential genetic determinants of young sudden unexplained death victims with suspected arrhythmogenic mitral valve prolapse syndrome.
Heart rhythm O2 20210722 5
<h4>Background</h4>Mitral valve prolapse (MVP) is largely considered a benign condition. However, MVP is over-represented consistently in sudden unexplained death in the young (SUDY) cohorts.<h4>Objective</h4>To determine the prevalence and potential genetic underpinnings of suspected arrhythmogenic MVP in a referral cohort of SUDY cases.<h4>Methods</h4>In this retrospective study, medical records/autopsy reports and whole exome molecular autopsy (WEMA) results for 77 SUDY victims (27 female; av ...[more]
