Browsing by Author "Groh, William J."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel
    (Public Library of Science (PloS), 2015) Celestino-Soper, Patrícia B. S.; Doytchinova, Anisiia; Steiner, Hillel A.; Uradu, Andrea; Lynnes, Ty C.; Groh, William J.; Miller, John M.; Lin, Hai; Gao, Hongyu; Wang, Zhiping; Liu, Yunlong; Chen, Peng-Sheng; Vatta, Matteo; Department of Medical and Molecular Genetics, IU School of Medicine
    BACKGROUND: The etiology of conduction disturbances necessitating permanent pacemaker (PPM) implantation is often unknown, although familial aggregation of PPM (faPPM) suggests a possible genetic basis. We developed a pan-cardiovascular next generation sequencing (NGS) panel to genetically characterize a selected cohort of faPPM. MATERIALS AND METHODS: We designed and validated a custom NGS panel targeting the coding and splicing regions of 246 genes with involvement in cardiac pathogenicity. We enrolled 112 PPM patients and selected nine (8%) with faPPM to be analyzed by NGS. RESULTS: Our NGS panel covers 95% of the intended target with an average of 229x read depth at a minimum of 15-fold depth, reaching a SNP true positive rate of 98%. The faPPM patients presented with isolated cardiac conduction disease (ICCD) or sick sinus syndrome (SSS) without overt structural heart disease or identifiable secondary etiology. Three patients (33.3%) had heterozygous deleterious variants previously reported in autosomal dominant cardiac diseases including CCD: LDB3 (p.D117N) and TRPM4 (p.G844D) variants in patient 4; TRPM4 (p.G844D) and ABCC9 (p.V734I) variants in patient 6; and SCN5A (p.T220I) and APOB (p.R3527Q) variants in patient 7. CONCLUSION: FaPPM occurred in 8% of our PPM clinic population. The employment of massive parallel sequencing for a large selected panel of cardiovascular genes identified a high percentage (33.3%) of the faPPM patients with deleterious variants previously reported in autosomal dominant cardiac diseases, suggesting that genetic variants may play a role in faPPM.
  • Thumbnail Image
    Item
    Heart Rate Variability Declines with Increasing Age and CTG Repeat Length in Patients with Myotonic Dystrophy Type 1
    (Wiley, 2003-07) Hardin, Bradley A.; Lowe, Miriam R.; Bhakta, Deepak; Groh, William J.; Medicine, School of Medicine
    Background: Cardiac myopathy manifesting as arrhythmias is common in the neurological disease, myotonic dystrophy type 1 (DM1). The purpose of the present study was to evaluate heart rate variability (HRV) in patients with DM1. Methods: In a multicenter study, history, ECG, and genetic testing were performed in DM1 patients. Results: In 289 patients in whom the diagnosis of DM1 was confirmed by a prolonged cytosine-thymine-guanine (CTG) repeat length the most common ambulatory ECG abnormality was frequent ventricular ectopy (16.3%). The 24-hour time domain parameters of SDNN (SD of the NN interval) and SDANN (SD of the mean NN, 5-minute interval) declined as age and CTG repeat length increased (SDNN: −8.5 ms per decade, 95% confidence intervals [CI]−12.9, −4.2, −8.7 ms per 500 CTG repeats, CI −15.7, −1.8, r = 0.24, P < 0.001; SDANN: −8.1 ms per decade, CI −12.4, −3.8, −8.8 ms per 500 CTG repeats, CI −15.7, −1.9, r = 0.23, P < 0.001). Short-term frequency domain parameters declined with age only (total power: −658 ms2 per decade, CI: −984, −331, r = 0.23, P < 0.001; low frequency (LF) power −287 ms2 per decade, CI: −397, −178, r = 0.30, P < 0.001; high frequency (HF) power: −267 ms2 per decade, CI: −386, −144, r = 0.25, P < 0.001). The LF/HF ratio increased as the patient aged (0.5 per decade, CI: 0.1, 0.9, r = 0.13, P = 0.03). Conclusions: In DM1 patients a decline in HRV is observed as the patient ages and CTG repeat length increases.