000061977 001__ 61977
000061977 005__ 20190709135524.0
000061977 0247_ $$2doi$$a10.1371/journal.pone.0181465
000061977 0248_ $$2sideral$$a100804
000061977 037__ $$aART-2017-100804
000061977 041__ $$aeng
000061977 100__ $$aMademont-Soler, I.
000061977 245__ $$aAdditional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy
000061977 260__ $$c2017
000061977 5060_ $$aAccess copy available to the general public$$fUnrestricted
000061977 5203_ $$aIntroduction: Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Methods: Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. Results: The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN. Conclusions: A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM.
000061977 536__ $$9info:eu-repo/grantAgreement/ES/FIS/BA16-00032$$9info:eu-repo/grantAgreement/ES/FIS/PI14-01773$$9info:eu-repo/grantAgreement/ES/FIS/PI15-02222
000061977 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000061977 590__ $$a2.766$$b2017
000061977 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 64 = 0.234$$c2017$$dQ1$$eT1
000061977 592__ $$a1.164$$b2017
000061977 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2017$$dQ1
000061977 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000061977 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2017$$dQ1
000061977 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000061977 700__ $$aMates, J.
000061977 700__ $$aYotti, R.
000061977 700__ $$aEspinosa, M.A.
000061977 700__ $$aPérez-Serra, A.
000061977 700__ $$aFernandez-Avila, A.I.
000061977 700__ $$aColl, M.
000061977 700__ $$aMéndez, I.
000061977 700__ $$aIglesias, A.
000061977 700__ $$aDel Olmo, B.
000061977 700__ $$aRiuró, H.
000061977 700__ $$aCuenca, S.
000061977 700__ $$aAllegue, C.
000061977 700__ $$aCampuzano, O.
000061977 700__ $$aPicó, F.
000061977 700__ $$aFerrer-Costa, C.
000061977 700__ $$aÁlvarez, P.
000061977 700__ $$aCastillo, S.
000061977 700__ $$aGarcia-Pavia, P.
000061977 700__ $$aGonzalez-Lopez, E.
000061977 700__ $$aPadron-Barthe, L.
000061977 700__ $$aDe Bustamante, A.D.
000061977 700__ $$aDarnaude, M.T.
000061977 700__ $$aGonzález-Hevia, J.I.
000061977 700__ $$aBrugada, J.
000061977 700__ $$aFernandez-Aviles, F.
000061977 700__ $$aBrugada, R.
000061977 773__ $$g12, 8 (2017), [23 pp]$$pPLoS One$$tPloS one$$x1932-6203
000061977 8564_ $$s632780$$uhttps://zaguan.unizar.es/record/61977/files/texto_completo.pdf$$yVersión publicada
000061977 8564_ $$s14012$$uhttps://zaguan.unizar.es/record/61977/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000061977 909CO $$ooai:zaguan.unizar.es:61977$$particulos$$pdriver
000061977 951__ $$a2019-07-09-11:58:56
000061977 980__ $$aARTICLE