TY - JOUR
T1 - Copy number variants in hypoplastic right heart syndrome
AU - Giannakou, Andreas
AU - Sicko, Robert J.
AU - Kay, Denise M.
AU - Zhang, Wei
AU - Romitti, Paul A.
AU - Caggana, Michele
AU - Shaw, Gary M.
AU - Jelliffe-Pawlowski, Laura L.
AU - Mills, James L.
N1 - Publisher Copyright:
Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
PY - 2018/12
Y1 - 2018/12
N2 - Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdeveloped and malformed structures of the right heart. Familial recurrence of HRHS indicates genetic factors contribute to its etiology. Our study investigates the presence of copy number variants (CNVs) in HRHS cases. We genotyped 42 HRHS cases identified from live births throughout California (2003–2010) using the Illumina HumanOmni2.5-8 array. We identified 14 candidate CNVs in 14 HRHS cases (33%) based on the genes included in the CNVs and their functions. Duplications overlapping part of ERBB4 were identified in two unrelated cases. ERBB4 is a neuregulin receptor with a pivotal role in cardiomyocyte differentiation and heart development. We also described a 7.5 Mb duplication at 16q11-12. Multiple genes in the duplicated region have previously been linked to heart defects and cardiac development, including RPGRIP1L, RBL2, SALL1, and MYLK3. Of the 14 validated CNVs, we identified four CNVs in close proximity to genes linked to the Wnt signaling pathway. This study expands on our previous work supporting the role of genetics in HRHS. We identified CNVs affecting crucial genes and signaling pathways involved in right heart development. ERBB4 and duplication of the 16q11-12 region are important areas for future investigation.
AB - Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdeveloped and malformed structures of the right heart. Familial recurrence of HRHS indicates genetic factors contribute to its etiology. Our study investigates the presence of copy number variants (CNVs) in HRHS cases. We genotyped 42 HRHS cases identified from live births throughout California (2003–2010) using the Illumina HumanOmni2.5-8 array. We identified 14 candidate CNVs in 14 HRHS cases (33%) based on the genes included in the CNVs and their functions. Duplications overlapping part of ERBB4 were identified in two unrelated cases. ERBB4 is a neuregulin receptor with a pivotal role in cardiomyocyte differentiation and heart development. We also described a 7.5 Mb duplication at 16q11-12. Multiple genes in the duplicated region have previously been linked to heart defects and cardiac development, including RPGRIP1L, RBL2, SALL1, and MYLK3. Of the 14 validated CNVs, we identified four CNVs in close proximity to genes linked to the Wnt signaling pathway. This study expands on our previous work supporting the role of genetics in HRHS. We identified CNVs affecting crucial genes and signaling pathways involved in right heart development. ERBB4 and duplication of the 16q11-12 region are important areas for future investigation.
KW - chromosome 16
KW - congenital heart defects
KW - copy number variants
KW - heart development
KW - hypoplastic right heart
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U2 - 10.1002/ajmg.a.40527
DO - 10.1002/ajmg.a.40527
M3 - Article
C2 - 30289599
AN - SCOPUS:85054522537
SN - 1552-4825
VL - 176
SP - 2760
EP - 2767
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 12
ER -