NICHD-California Birth Defects Study

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications, trials & patents

Abstract

We have expanded our collaboration with The California Department of Health and Stanford Universiy. The first laboratory report, assaying copy number variants in classic heterotaxy cases was published. 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. These findings have been reported in Human Genetics. Cases with Ebstein anomaly and hypoplastic right heart syndrome from California have been identified, samples selected and assayed to identify copy number variants. The analysis is underway. This study is being expanded since additional funding has become available 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. This additional work has received IRB approval in California and exemption at NIH and is awaiting permission from the State of California to receive biospecimens. Samples are being identified in NY State.