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Novel LVNC genetic aetiology discovered by an original whole-exome sequencing data combinatory filtering method

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dc.creatorGallo Bernal, Sspa
dc.creatorCarlosama, C.spa
dc.creatorMedina, H.spa
dc.creatorContreras, J.spa
dc.creatorCabrera, R.spa
dc.creatorForero, J.F.spa
dc.creatorHuertas Quiñones, Víctor Manuelspa
dc.creatorTorres, A.spa
dc.creatorLaissue, P.spa
dc.date.accessioned2020-08-06T16:24:06Z
dc.date.available2020-08-06T16:24:06Z
dc.date.created2019-04spa
dc.description.abstractBackground: Left ventricular non-compaction (LVNC) is a cardiomyopathy characterized by deep intra-trabecular recesses and prominent left ventricular trabeculae. This cardiomyopathy has remarkable phenotypic and genetic heterogeneity. Its molecular diagnosis via next generation sequencing is challenging due to the large amount of potential aetiological variants, especially in complex cases originating from mutations in various genes. Objectives: This study sought to determine a novel diagnostic approach for identifying the molecular cause of LVNC in patients showing intra-familial phenotype variability and evoking a digenic aetiology. Methods: We performed whole-exome sequencing (WES) in a three-generation family of patients affected by different degrees of LVNC. An enriched subset of 94 LVNC candidate genes was analysed in silico using an original WES data combinatory filtering method. Results: We identified two novel heterozygous mutations, one in ACTC1 (c.740G>A; p.Gly247Asp) and another in ITGA7 (c.3280C>T; p.Gln1094Ter) which perfectly segregated with the phenotype. These variants underlined the disease’s digenic origin, explaining intra-familial phenotype variability. We unambiguously determined that ITGA7 mutations lead to LVNC. Conclusions: The results argues in favour of the final common hypothesis proposed as being involved in complex heterogeneous cardiovascular diseases. The genomic/computational approach presented here is an advantageous and efficient method for dissecting the molecular basis of LVNC’s origin and we strongly recommend it for diagnostic/prognostic purposes. We have described the direct association of an ITGA7 mutation and LVNC pathophysiology for the first time, thereby enriching the repertoire of genes to be systematically analysed in LVNC patients.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1017/s1047951119000489
dc.identifier.issnISSN: 1047-9511
dc.identifier.issnEISSN: 1467-1107
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/26458
dc.language.isoengspa
dc.publisherCambridge University Pressspa
dc.relation.citationEndPages196
dc.relation.citationIssueNo. S1
dc.relation.citationStartPages1
dc.relation.citationTitleCardiology in the Young;53rd Annual Meeting of the Association for European Paediatric and Congenital Cardiology (AEPC) Fibes–Conference and Exhibition Centre, Seville, Spain;May 15–18, 2019
dc.relation.citationVolumeVol. 29
dc.relation.ispartofCardiology in the Young, ISSN: 1047-9511 ; EISSN: 1467-1107, Vol.29, No.S1 (2019-04); pp.s1-s196spa
dc.relation.ispartofAnnual Meeting of the Association for European Paediatric and Congenital Cardiology (AEPC) Fibes–Conference and Exhibition Centre, Seville, Spain (May 15–18, 2019); O51spa
dc.relation.urihttps://www.cambridge.org/core/services/aop-cambridge-core/content/view/A11D3D0EC9C01A596C63455DCB351887/S1047951119000489a.pdf/div-class-title-53rd-annual-meeting-of-the-association-for-european-paediatric-and-congenital-cardiology-aepc-fibes-conference-and-exhibition-centre-seville-spain-may-15-18-2019-div.pdfspa
dc.rights.accesRightsinfo:eu-repo/semantics/closedAccess
dc.rights.accesoBloqueado (Texto referencial)spa
dc.sourceCardiology in the Youngspa
dc.source53rd Annual Meeting of the Association for European Paediatric and Congenital Cardiology (AEPC) Fibes–Conference and Exhibition Centre, Seville, Spainspa
dc.sourceMay 15–18, 2019spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subject.keywordCardiorespiratory Medicine and Haematologyspa
dc.subject.keywordMedical and Health Sciencesspa
dc.titleNovel LVNC genetic aetiology discovered by an original whole-exome sequencing data combinatory filtering methodspa
dc.title.TranslatedTitleNueva etiología genética de LVNC descubierta por un método de filtrado combinatorio de datos de secuenciación de exoma completo originalspa
dc.typeconferenceObjecteng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaDocumento de conferenciaspa
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