Browsing by Subject "HEART"
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Item Open Access Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among Greater Middle Eastern individuals reveals a novel homozygous variant associated with neonatal dilated cardiomyopathy.(Scientific reports, 2019-06-21) Jones, Edward G; Mazaheri, Neda; Maroofian, Reza; Zamani, Mina; Seifi, Tahereh; Sedaghat, Alireza; Shariati, Gholamreza; Jamshidi, Yalda; Allen, Hugh D; Wehrens, Xander HT; Galehdari, Hamid; Landstrom, Andrew PJunctophilin-2 (JPH2) is a part of the junctional membrane complex that facilitates calcium-handling in the cardiomyocyte. Previously, missense variants in JPH2 have been linked to hypertrophic cardiomyopathy; however, pathogenic "loss of function" (LOF) variants have not been described. Family-based genetic analysis of GME individuals with cardiomyopathic disease identified an Iranian patient with dilated cardiomyopathy (DCM) as a carrier of a novel, homozygous single nucleotide insertion in JPH2 resulting in a stop codon (JPH2-p.E641*). A second Iranian family with consanguineous parents hosting an identical heterozygous variant had 2 children die in childhood from cardiac failure. To characterize ethnicity-dependent genetic variability in JPH2 and to identify homozygous JPH2 variants associated with cardiac disease, we identified variants in JPH2 in a worldwide control cohort (gnomAD) and 2 similar cohorts from the Greater Middle East (GME Variome, Iranome). These were compared against ethnicity-matched clinical whole exome sequencing (WES) referral tests and a case cohort of individuals with hypertrophic cardiomyopathy (HCM) based on comprehensive review of the literature. Worldwide, 1.45% of healthy individuals hosted a rare JPH2 variant with a significantly higher proportion among GME individuals (4.45%); LOF variants were rare overall (0.04%) yet were most prevalent in GME (0.21%). The increased prevalence of LOF variants in GME individuals was corroborated among region-specific, clinical WES cohorts. In conclusion, we report ethnic-specific differences in JPH2 rare variants, with GME individuals being at higher risk of hosting homozygous LOF variants. This conclusion is supported by the identification of a novel JPH2 LOF variant confirmed by segregation analysis resulting in autosomal recessive pediatric DCM due to presumptive JPH2 truncation.Item Open Access Evaluation of a Standardized Cardiac Athletic Screening for National Collegiate Athletic Association (NCAA) Athletes.(The western journal of emergency medicine, 2019-08-14) Fischetti, Chanel E; Kamyszek, Reed W; Shaheen, Stephen; Oshlag, Benjamin; Banks, Adam; Blood, AJ; Bytomski, Jeffrey R; Boggess, Blake; Lahham, ShadiINTRODUCTION:Sudden cardiac death is a rare cause of death in young athletes. Current screening techniques include history and physical exam (H and P), with or without an electrocardiogram (ECG). Adding point of care cardiac ultrasound has demonstrated benefits, but there is limited data about implementing this technology. We evaluated the feasibility of adding ultrasound to preparticipation screening for collegiate athletes. METHODS:We prospectively enrolled 42 collegiate athletes randomly selected from several sports. All athletes were screened using a 14-point H and P based on 2014 American College of Cardiology (ACC) and American Heart Association (AHA) guidelines, ECG, and cardiac ultrasound. RESULTS:We screened 11 female and 31 male athletes. On ultrasound, male athletes demonstrated significantly larger interventricular septal wall thickness (p = 0.002), posterior wall thickness (p <0.001) and aortic root breadth (p = 0.002) compared to females. Based on H and P and ECGs alone and a combination of H and P with ECG, no athletes demonstrated a positive screening for cardiac abnormalities. However, with combined H and P, ECG, and cardiac ultrasound, one athlete demonstrated positive findings. CONCLUSIONS:We believe that adding point of care ultrasound to the preparticipation exam of college athletes is feasible. This workflow may provide a model for athletic departments' screening.Item Open Access The CapZ interacting protein Rcsd1 is required for cardiogenesis downstream of Wnt11a in Xenopus laevis(Developmental Biology, 2017-04) Hempel, Annemarie; Kühl, Susanne J; Rothe, Melanie; Rao Tata, Purushothama; Sirbu, Ioan Ovidiu; Vainio, Seppo J; Kühl, Michael