Abstract
Neural tube defects (NTDs) remain one of the most serious birth defects, and although genes in several pathways have been implicated as risk factors for neural tube defects via knockout mouse models, very few molecular causes in humans have been identified. Whole exome sequencing identified deleterious variants in key apoptotic genes in two families with recurrent neural tube defects. Functional studies in fibroblasts indicate that these variants are loss-of-function, as apoptosis is significantly reduced. This is the first report of variants in apoptotic genes contributing to neural tube defect risk in humans.
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Acknowledgements
Funding for this work included grants from the South Carolina Department of Health and Environmental Control (SCDHEC), the South Carolina Department of Disabilities and Special Needs (SCDDSN), the National Institute of General Medical Sciences (NIH R01Gm93937, NIGMS), and the GGC Foundation. We would also like to thank the patients and their families for their participation in this study and recognize the contributions of our laboratory staff and the clinical team at the Greenwood Genetic Center for their considerable efforts.
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Spellicy, C., Norris, J., Bend, R. et al. Key apoptotic genes APAF1 and CASP9 implicated in recurrent folate-resistant neural tube defects. Eur J Hum Genet 26, 420–427 (2018). https://doi.org/10.1038/s41431-017-0025-y
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DOI: https://doi.org/10.1038/s41431-017-0025-y
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