Key result
Next-Generation Sequencing yielded a significantly higher mutation detection rate in early-onset compared to late-onset hypertrophic cardiomyopathy patients (85.7% vs 22.9%, p<0.0001).
Why the study?
Does Next-Generation Sequencing yield different mutation detection rates in early-onset versus late-onset hypertrophic cardiomyopathy patients?
Cohort (n=70)
Does Next-Generation Sequencing yield different mutation detection rates in early-onset versus late-onset hypertrophic cardiomyopathy patients?
Next-Generation Sequencing provides a high diagnostic yield in early-onset HCM and those with a family history, suggesting targeted genetic testing is highly effective in these subgroups.
Answers are grounded in this paper and cite their sources.
NGS panels may boost diagnostic yield in early-onset HCM with family history; supports refined selection criteria but leaves broader adoption open pending validation.
Sequencing of sarcomere protein genes in patients fulfilling the clinical diagnostic criteria for hypertrophic cardiomyopathy (HCM) identifies a disease-causing mutation in 35% to 60% of cases. Age at diagnosis and family history may increase the yield of mutations screening. In order to assess whether Next-Generation Sequencing (NGS) may fulfil the molecular diagnostic needs in HCM, we included 17 HCM-related genes in a sequencing panel run on PGM IonTorrent. We selected 70 HCM patients, 35 with early (≤25 years) and 35 with late (≥65 years) diagnosis of disease onset. All samples had a 98.6% average of target regions, with coverage higher than 20× (mean coverage 620×). We identified 41 different mutations (seven of them novel) in nine genes: MYBPC3 (17/41 = 41%); MYH7 (10/41 = 24%); TNNT2, CAV3 and MYH6 (3/41 = 7.5% each); TNNI3 (2/41 = 5%); GLA, MYL2, and MYL3 (1/41=2.5% each). Mutation detection rate was 30/35 (85.7%) in early-onset and 8/35 (22.9%) in late-onset HCM patients, respectively (p < 0.0001). The overall detection rate for patients with positive family history was 84%, and 90.5% in patients with early disease onset. In our study NGS revealed higher mutations yield in patients with early onset and with a family history of HCM. Appropriate patient selection can increase the yield of genetic testing and make diagnostic testing cost-effective.
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Rubattu et al. (2016) conducted a cohort in Hypertrophic cardiomyopathy (HCM) (n=70). Early disease onset (≤25 years) vs. Late disease onset (≥65 years) was evaluated on Mutation detection rate (p=< 0.0001). Next-Generation Sequencing yielded a significantly higher mutation detection rate in early-onset compared to late-onset hypertrophic cardiomyopathy patients (85.7% vs 22.9%, p<0.0001).
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