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Int. J. Mol. Sci. 2016, 17(8), 1239;

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

Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, 00185 Rome, Italy
Department of Angiocardioneurology, IRCCS Neuromed, 86077 Pozzilli, Italy
These authors contributed equally to this work.
Present address: Universitatsklinik fur Kardiologie, Inselspital, Freiburgstrasse 4, 3010 Bern, Switzerland.
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
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)
Full-Text   |   PDF [229 KB, uploaded 30 July 2016]


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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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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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