Genetic Factors in Birth Defects

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications, trials & patents

Abstract

DNA has been obtained from approximately 20 major malformations for current and future investigations. We have recently expanded our investigations to include searching for copy number variants in rare defects. New York has an exceptionally valuable research resource in having approximately 250,000 births per year from which to identify children with rare defects. In addition to classic candidate gene approaches, cases have been selected for copy number variant studies. The laboratory work has now been completed on many of the conditions selected for copy number variant testing. Copy number variants have been identified in several conditions of interest. We have now published findings on heterotaxy and on posterior urethral valves demonstrating copy number variants of potential importance in both conditions and providing leads for future research. Copy number variant analyses have been completed and published recently for Klippel Trenaunay Syndrome and split hand/foot malformation . Our collaboration with the CDC's National Birth Defects Prevention Study and Dr. Paul Romitti at the University of Iowa is currently examining genetic data for associations with choanal atresia, a defect in which the nasal passages fail to develop normally. This study involves testing samples from New York State and from the collaborative group that formed the National Birth Defects Prevention Study. Following up on our work on craniosynostosis (see Justice et al. Nature Genetics), we are preparing samples to examine more types. The previous work focused on saggital craniosynostosis. These collaborations will expand on this to look for genetic factors associated with defects in other sutures. This work has received external funding and is ongoing. We have established a collaboration with the Statens Serum Institut in Copenhagen, Denmark to examine genetic factors in congenital hydrocephalus. We have identified samples for confirmatory testing of SNPs from their GWAS study. Laboratory analysis is complete. We are beginning a new investigation of sacral agenesis using whole exome sequencing in collaboration with the CDC's National Birth Defects Prevention Study. We will also collaborate with the University of Iowa to examine genetic risk factors in club foot. We are setting up a study with the University of Iowa to examine risk factors in oral cleft cases.