TY - JOUR
T1 - Copy-number variant analysis of classic heterotaxy highlights the importance of body patterning pathways
AU - Hagen, Erin M.
AU - Sicko, Robert J.
AU - Kay, Denise M.
AU - Rigler, Shannon L.
AU - Dimopoulos, Aggeliki
AU - Ahmad, Shabbir
AU - Doleman, Margaret H.
AU - Fan, Ruzong
AU - Romitti, Paul A.
AU - Browne, Marilyn L.
AU - Caggana, Michele
AU - Brody, Lawrence C.
AU - Shaw, Gary M.
AU - Jelliffe-Pawlowski, Laura L.
AU - Mills, James L.
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg (outside the USA).
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Classic heterotaxy consists of congenital heart defects with abnormally positioned thoracic and abdominal organs. We aimed to uncover novel, genomic copy-number variants (CNVs) in classic heterotaxy cases. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 infants (cases) with classic heterotaxy identified from California live births from 1998 to 2009. CNVs were identified using the PennCNV software. We identified 56 rare CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, not previously linked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and near MIR302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axes determination. FGF12, RBFOX1, and MIR302F could be important in human heterotaxy, because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIR302F is warranted.
AB - Classic heterotaxy consists of congenital heart defects with abnormally positioned thoracic and abdominal organs. We aimed to uncover novel, genomic copy-number variants (CNVs) in classic heterotaxy cases. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 infants (cases) with classic heterotaxy identified from California live births from 1998 to 2009. CNVs were identified using the PennCNV software. We identified 56 rare CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, not previously linked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and near MIR302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axes determination. FGF12, RBFOX1, and MIR302F could be important in human heterotaxy, because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIR302F is warranted.
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U2 - 10.1007/s00439-016-1727-x
DO - 10.1007/s00439-016-1727-x
M3 - Article
C2 - 27637763
AN - SCOPUS:84988409855
SN - 0340-6717
VL - 135
SP - 1355
EP - 1364
JO - Human Genetics
JF - Human Genetics
IS - 12
ER -