A next-generation sequencing approach to identify gene mutations in early- and late-onset hypertrophic cardiomyopathy patients of an Italian cohort

Speranza Rubattu, Cristina Bozzao, Ermelinda Pennacchini, Erika Pagannone, Beatricemaria Musumeci, Maria Piane, Aldo Germani, Camilla Savio, Pietro Francia, Massimo Volpe, Camillo Autore, Luciana Chessa

Research output: Contribution to journalArticlepeer-review

Abstract

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[1] (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.

Original languageEnglish
Article number1239
JournalInternational Journal of Molecular Sciences
Volume17
Issue number8
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Gene variants
  • Genetics
  • Hypertrophic cardiomyopathy
  • Next-generation sequencing

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

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