NICHD-California Birth Defects Study

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications & trials

Abstract

We have expanded our collaboration with The California Department of Health and Stanford Universiy. The first laboratory work, assaying copy number variants in classic heterotaxy cases was completed. The analysis is complete and data have been presented in abstract form. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 cases of classic heterotaxy identified from California live births from 1998-2009. CNVs were identified using PennCNV software. We identified 56 CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, previously unlinked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and MIRNA302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axis determination. FGF12, RBFOX1 and MIRNA302F 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 MIRNA302F is warranted. A paper has been prepared and submitted for publication. Additional samples from California have been identified, selected and the DNA extracted to look at other congenital heart defects. The samples have been genotyping for copy number variants. The data are currently being cleaned and edited for analysis. This study will be expanded, funding being available, in fiscal year 2017 to include other, rare, non-cardiac defects. Because of the very large number of births in California, we anticipate being able to identify cases of very rare defects for investigation. Because of our work in New York State, we also should be able to identify subjects from NY to verify findings from our investigations in California.