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...

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Autores Principales: Cabrera, Rodrigo, Miranda, Marta Catalina, Restrepo, Carlos Martin, Huertas-quiñones, Victor Manuel, Laissue, Paul, Tamar Silva, Claudia, Tomás Hernández, Camilo José, Quero, Rossi, Ortiz, Angela María, Programa Pinocchio
Formato: Objeto de conferencia (Conference Object)
Lenguaje:Inglés (English)
Publicado: Cambridge University Press 2017
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Acceso en línea:https://repository.urosario.edu.co/handle/10336/26456
https://doi.org/10.1017/s104795111700110x
id ir-10336-26456
recordtype dspace
spelling ir-10336-264562020-08-06T16:24:12Z Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly Identificación de variantes genéticas y anomalías cromosómicas asociadas con la anomalía de Ebstein. Cabrera, Rodrigo Miranda, Marta Catalina Restrepo, Carlos Martin Huertas-quiñones, Victor Manuel Laissue, Paul Tamar Silva, Claudia Tomás Hernández, Camilo José Quero, Rossi Ortiz, Angela María Programa Pinocchio Cardiorespiratory Medicine and Haematology Medical and Health Sciences 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. 2017-07 2020-08-06T16:24:05Z info:eu-repo/semantics/conferenceObject info:eu-repo/semantics/publishedVersion ISSN: 1047-9511 EISSN: 1467-1107 https://repository.urosario.edu.co/handle/10336/26456 https://doi.org/10.1017/s104795111700110x eng info:eu-repo/semantics/closedAccess application/pdf Cambridge University Press Cardiology in the Young 7th World Congress of Pediatric Cardiology & Cardiac Surgery Abstracts
institution EdocUR - Universidad del Rosario
collection DSpace
language Inglés (English)
topic Cardiorespiratory Medicine and Haematology
Medical and Health Sciences
spellingShingle Cardiorespiratory Medicine and Haematology
Medical and Health Sciences
Cabrera, Rodrigo
Miranda, Marta Catalina
Restrepo, Carlos Martin
Huertas-quiñones, Victor Manuel
Laissue, Paul
Tamar Silva, Claudia
Tomás Hernández, Camilo José
Quero, Rossi
Ortiz, Angela María
Programa Pinocchio
Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly
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.
format Objeto de conferencia (Conference Object)
author Cabrera, Rodrigo
Miranda, Marta Catalina
Restrepo, Carlos Martin
Huertas-quiñones, Victor Manuel
Laissue, Paul
Tamar Silva, Claudia
Tomás Hernández, Camilo José
Quero, Rossi
Ortiz, Angela María
Programa Pinocchio
author_facet Cabrera, Rodrigo
Miranda, Marta Catalina
Restrepo, Carlos Martin
Huertas-quiñones, Victor Manuel
Laissue, Paul
Tamar Silva, Claudia
Tomás Hernández, Camilo José
Quero, Rossi
Ortiz, Angela María
Programa Pinocchio
author_sort Cabrera, Rodrigo
title Identification of genetic variants and chromosomal abnormalities associated with Ebstein anomaly
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
publisher Cambridge University Press
publishDate 2017
url https://repository.urosario.edu.co/handle/10336/26456
https://doi.org/10.1017/s104795111700110x
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score 12,131701