Copy number variants in Ebstein anomaly

Andreas Giannakou; Wei Zhang; James L Mills; Robert J Sicko; Michele Caggana; Denise M Kay; Paul Romitti; Marilyn L Browne; Lawrence C Brody; Laura Jelliffe-Pawlowski; Gary M Shaw

doi:10.1371/journal.pone.0188168

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Copy number variants in Ebstein anomaly

Andreas Giannakou, Wei Zhang, James L Mills, Robert J Sicko, Michele Caggana, Denise M Kay, Paul Romitti, Marilyn L Browne, Lawrence C Brody, Laura Jelliffe-Pawlowski, …

PLoS One, Vol.12(12), pp.e0188168-e0188168

2017

DOI: 10.1371/journal.pone.0188168

PMCID: PMC5720705

PMID: 29216221

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Abstract

BACKGROUND: Ebstein anomaly (EA) is a rare congenital defect characterized by apical displacement of the septal tricuspid leaflets and atrialization of the right ventricle. The etiology of EA is unclear; however, recurrence in families and the association of EA with genetic syndromes and copy number variants (CNVs) suggest a genetic component.OBJECTIVE: We performed a population-based study to search for recurrent and novel CNVs in a previously unreported set of EA cases.METHODS: We genotyped 60 EA cases identified from all live births (2,891,076) from selected California counties (1991-2010) using the Illumina HumanOmni2.5-8 array. We identified 38 candidate CNVs in 28 (46%) cases and prioritized and validated 11 CNVs based on the genes included.RESULTS: Five CNVs (41%) overlapped or were close to genes involved in early myocardial development, including NODAL, PDLIM5, SIX1, ASF1A and FGF12. We also replicated a previous association of EA with CNVs at 1p34.1 and AKAP12. Finally, we identified four CNVs overlapping or in close proximity to the transcription factors HES3, TRIM71, CUX1 and EIF4EBP2.CONCLUSIONS: This study supports the relationship of genetic factors to EA and demonstrates that defects in cardiomyocytes and myocardium differentiation may play a role. Abnormal differentiation of cardiomyocytes and how genetic factors contribute should be examined for their association with EA.

Details

Title: Subtitle: Copy number variants in Ebstein anomaly
Creators: Andreas Giannakou
Wei Zhang
James L Mills
Robert J Sicko
Michele Caggana
Denise M Kay
Paul Romitti
Marilyn L Browne
Lawrence C Brody
Laura Jelliffe-Pawlowski
Gary M Shaw
Resource Type: Journal article
Publication Details: PLoS One, Vol.12(12), pp.e0188168-e0188168
DOI: 10.1371/journal.pone.0188168
PMID: 29216221
PMCID: PMC5720705
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: DOI: 10.13039/100009633, name: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Language: English
Date published: 2017
Academic Unit: Epidemiology; Biostatistics
Record Identifier: 9983995051202771

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