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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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 |
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EdocUR - Universidad del Rosario |
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Inglés (English) |
topic |
Cardiorespiratory Medicine and Haematology Medical and Health Sciences |
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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 |
_version_ |
1675439918284800000 |
score |
12,131701 |