TY - JOUR
T1 - Copy number variants in Ebstein anomaly
AU - Giannakou, Andreas
AU - Sicko, Robert J.
AU - Zhang, Wei
AU - Romitti, Paul
AU - Browne, Marilyn L.
AU - Caggana, Michele
AU - Brody, Lawrence C.
AU - Jelliffe-Pawlowski, Laura
AU - Shaw, Gary M.
AU - Kay, Denise M.
AU - Mills, James L.
N1 - Publisher Copyright:
© 2017, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0188168
DO - 10.1371/journal.pone.0188168
M3 - Article
C2 - 29216221
AN - SCOPUS:85037661409
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 12
M1 - e0188168
ER -