Hum Genet

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)\ua0signaling 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.U01 DD001033/DD/NCBDD CDC HHS/United StatesR01 HL092330/HL/NHLBI NIH HHS/United StatesHHSN275201100001I/HD/NICHD NIH HHS/United StatesHHSN275201100001C/HD/NICHD NIH HHS/United StatesN01DK73431/HD/NICHD NIH HHS/United StatesZ01 HD008792-01/Intramural NIH HHS/United StatesHHSN275201100001G/HD/NICHD NIH HHS/United States2017-12-01T00:00:00Z27637763PMC506578