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Open AccessArticle

A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort

1
Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, 00185 Rome, Italy
2
Department of Angiocardioneurology, IRCCS Neuromed, 86077 Pozzilli, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Present address: Universitatsklinik fur Kardiologie, Inselspital, Freiburgstrasse 4, 3010 Bern, Switzerland.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2016, 17(8), 1239; https://doi.org/10.3390/ijms17081239
Received: 16 June 2016 / Revised: 22 July 2016 / Accepted: 22 July 2016 / Published: 30 July 2016
(This article belongs to the Special Issue Next-Generation Sequencing for Clinical Application)
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. View Full-Text
Keywords: genetics; gene variants; hypertrophic cardiomyopathy; next-generation sequencing genetics; gene variants; hypertrophic cardiomyopathy; next-generation sequencing
MDPI and ACS Style

Rubattu, S.; Bozzao, C.; Pennacchini, E.; Pagannone, E.; Musumeci, B.M.; Piane, M.; Germani, A.; Savio, C.; Francia, P.; Volpe, M.; Autore, C.; Chessa, L. A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort. Int. J. Mol. Sci. 2016, 17, 1239.

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