Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly
Background/Hypothesis: Ebstein Anomaly (EA) is an infrequent congenital heart defect (CHD) with considerable phenotypic heterogeneity in which right ventricle, tricuspid valve and electrical abnormalities prevail. Phenotypic diversity likely reflects an underlying genetic heterogeneity, which combin...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2017
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/26456
- Acceso en línea:
- https://doi.org/10.1017/s104795111700110x
https://repository.urosario.edu.co/handle/10336/26456
- Palabra clave:
- Cardiorespiratory Medicine and Haematology
Medical and Health Sciences
- Rights
- License
- http://purl.org/coar/access_right/c_14cb
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Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomalyIdentificación de variantes genéticas y anomalías cromosómicas asociadas con la anomalía de Ebstein.Cardiorespiratory Medicine and HaematologyMedical and Health SciencesBackground/Hypothesis: Ebstein Anomaly (EA) is an infrequent congenital heart defect (CHD) with considerable phenotypic heterogeneity in which right ventricle, tricuspid valve and electrical abnormalities prevail. Phenotypic diversity likely reflects an underlying genetic heterogeneity, which combined with studies based on small cohorts, has hindered high-confidence associations with genetic variants. Although a few chromosomal abnormalities and mutations have been linked to the disease, genetic etiologies have not been identified in most cases. Our Cardiovascular Care Center, a referral institution for CHD, has an unusually large cohort of EA patients that allows a comprehensive study of EA genetics. Materials and Methods: We carried out a thorough phenotypic characterization of 147 EA patients, followed by unsupervised two-step cluster analysis to classify patients according to the presence or absence of comorbidities. Selected syndromic/familial cases were subjected to whole exome sequencing and/or comparative genomic hybridization. Variant filtering was accomplished using family members to identify high confidence associations with identified variants. Results: In the cohort analysis, we identified a large proportion of syndromic (10.9%) and familial cases (11.6%). Molecular testing revealed high likelihood causative variants/abnormalities in most of the syndromic/familial cases studied. Our results suggest a novel association of EA with a rare chromosomal abnormality, the identification of a single gene in the 1p36 EA-associated region, as well as novel variants in familial cases with high likelihood of causality. Cluster analysis identified homogeneous endophenotypes that possibly reflect different underlying genetic etiologies. We are currently expanding our analysis to isolated cases. Conclusions: Our data suggest that major causative genetic variants/ chromosomal abnormalities can be found in a significant proportion of EA cases with thorough phenotypic evaluations and genome-scale molecular testing, raising the possibility of a role for genetic testing in the management of EA.Cambridge University Press2017-072020-08-06T16:24:05Zinfo:eu-repo/semantics/conferenceObjecthttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_c94fapplication/pdfhttps://doi.org/10.1017/s104795111700110xISSN: 1047-9511EISSN: 1467-1107https://repository.urosario.edu.co/handle/10336/26456Cardiology in the Young7th World Congress of Pediatric Cardiology & Cardiac Surgery Abstractsinstname:Universidad del Rosarioreponame:Repositorio Institucional EdocURenghttps://www.cambridge.org/core/services/aop-cambridge-core/content/view/9E812D0EB5A2C33365174EBF430B255C/S104795111700110Xa.pdf/7th_world_congress_of_pediatric_cardiology_cardiac_surgery_abstracts.pdf#page=109http://purl.org/coar/access_right/c_14cbCabrera, RodrigoMiranda, Marta CatalinaHuertas-quiñones, Victor ManuelLaissue, PaulTamar Silva, ClaudiaTomás Hernández, Camilo JoséQuero, RossiOrtiz, Angela MaríaPrograma PinocchioRestrepo Fernández, Carlos Martínoai:repository.urosario.edu.co:10336/264562021-06-03T00:51:05Z |
dc.title.none.fl_str_mv |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly Identificación de variantes genéticas y anomalías cromosómicas asociadas con la anomalía de Ebstein. |
title |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly |
spellingShingle |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly Cardiorespiratory Medicine and Haematology Medical and Health Sciences |
title_short |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly |
title_full |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly |
title_fullStr |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly |
title_full_unstemmed |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly |
title_sort |
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly |
dc.subject.none.fl_str_mv |
Cardiorespiratory Medicine and Haematology Medical and Health Sciences |
topic |
Cardiorespiratory Medicine and Haematology Medical and Health Sciences |
description |
Background/Hypothesis: Ebstein Anomaly (EA) is an infrequent congenital heart defect (CHD) with considerable phenotypic heterogeneity in which right ventricle, tricuspid valve and electrical abnormalities prevail. Phenotypic diversity likely reflects an underlying genetic heterogeneity, which combined with studies based on small cohorts, has hindered high-confidence associations with genetic variants. Although a few chromosomal abnormalities and mutations have been linked to the disease, genetic etiologies have not been identified in most cases. Our Cardiovascular Care Center, a referral institution for CHD, has an unusually large cohort of EA patients that allows a comprehensive study of EA genetics. Materials and Methods: We carried out a thorough phenotypic characterization of 147 EA patients, followed by unsupervised two-step cluster analysis to classify patients according to the presence or absence of comorbidities. Selected syndromic/familial cases were subjected to whole exome sequencing and/or comparative genomic hybridization. Variant filtering was accomplished using family members to identify high confidence associations with identified variants. Results: In the cohort analysis, we identified a large proportion of syndromic (10.9%) and familial cases (11.6%). Molecular testing revealed high likelihood causative variants/abnormalities in most of the syndromic/familial cases studied. Our results suggest a novel association of EA with a rare chromosomal abnormality, the identification of a single gene in the 1p36 EA-associated region, as well as novel variants in familial cases with high likelihood of causality. Cluster analysis identified homogeneous endophenotypes that possibly reflect different underlying genetic etiologies. We are currently expanding our analysis to isolated cases. Conclusions: Our data suggest that major causative genetic variants/ chromosomal abnormalities can be found in a significant proportion of EA cases with thorough phenotypic evaluations and genome-scale molecular testing, raising the possibility of a role for genetic testing in the management of EA. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-07 2020-08-06T16:24:05Z |
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info:eu-repo/semantics/conferenceObject |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_c94f |
dc.identifier.none.fl_str_mv |
https://doi.org/10.1017/s104795111700110x ISSN: 1047-9511 EISSN: 1467-1107 https://repository.urosario.edu.co/handle/10336/26456 |
url |
https://doi.org/10.1017/s104795111700110x https://repository.urosario.edu.co/handle/10336/26456 |
identifier_str_mv |
ISSN: 1047-9511 EISSN: 1467-1107 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
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https://www.cambridge.org/core/services/aop-cambridge-core/content/view/9E812D0EB5A2C33365174EBF430B255C/S104795111700110Xa.pdf/7th_world_congress_of_pediatric_cardiology_cardiac_surgery_abstracts.pdf#page=109 |
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application/pdf |
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Cambridge University Press |
publisher.none.fl_str_mv |
Cambridge University Press |
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Cardiology in the Young 7th World Congress of Pediatric Cardiology & Cardiac Surgery Abstracts instname:Universidad del Rosario reponame:Repositorio Institucional EdocUR |
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Universidad del Rosario |
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Universidad del Rosario |
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