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首页> 外文期刊>International Journal of Molecular Sciences >A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort
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A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort

机译：下一代测序方法，用于识别意大利人群的早发型和晚发型肥厚型心肌病患者的基因突变

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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.
机译：满足肥厚型心肌病（HCM）临床诊断标准的患者中的肌小节蛋白基因测序可在35％至60％的病例中识别出致病突变。诊断时的年龄和家族史可能会增加突变筛查的产率。为了评估下一代测序（NGS）是否可以满足HCM中的分子诊断需求，我们在PGM IonTorrent上运行的测序小组中纳入了17个HCM相关基因。我们选择了70例HCM患者，其中35例早期（≤25岁）和35例晚期（≥65岁）被诊断为疾病发作。所有样本的目标区域平均值平均为98.6％，覆盖率高于20倍（平均覆盖率620倍）。我们在9个基因中鉴定出41个不同的突变（其中7个是新突变）：MYBPC3（17/41 = 41％）; MYH7（10/41 = 24％）; TNNT2，CAV3和MYH6（3/41 = 7.5％各自）; TNNI3（2/41 = 5％）; GLA，MYL2和MYL3（分别为1/41 = 2.5％）。早发HCM患者的突变检出率分别为30/35（85.7％）和晚发HCM患者的8/35（22.9％）（p <0.0001）。家族史阳性患者的总检出率为84％，疾病早期发作的患者总检出率为90.5％。在我们的研究中，NGS揭示了发病较早且有HCM家族史的患者中突变产生率更高。适当的患者选择可以提高基因检测的产率，并使诊断检测具有成本效益。

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