Purpose: Spina bifida (SB) arises from complex genetic interactions that converge to interfere with neural tube closure. Understanding the precise patterns conferring SB risk requires a deep exploration of the genomic networks and molecular pathways that govern neurulation. This study aims to delineate genome-wide regulatory signatures underlying SB pathophysiology.
Methods: An untargeted, genome-wide approach was used to interrogate regulatory regions for rare single-nucleotide and copy-number variants (rSNVs and rCNVs, respectively) predicted to affect gene expression, comparing results from SB patients with healthy controls. Qualifying variants were subjected to a deep learning prioritization framework to identify the most functionally relevant variants, as well as the likely target genes affected by these rare regulatory variants.
Results: This ensemble of computational tools identified rSNVs in specific transcription factor binding sites (TFBSs) that distinguish SB cases from controls. rSNV enrichment was found in specific TFBSs, especially CCCTC-binding factor binding sites. These TFBSs were subjected to a deep learning prioritization framework to identify the most functionally relevant variants, as well as the likely target genes affected by these rSNVs. The functional pathways or modules implicated by these regulated genes serve protein transport, cilia assembly, and central nervous system development. Moreover, the detected rare copy-number variants in SB cases are positioned to disrupt gene regulatory networks and alter 3-dimensional genomic architectures, including brain-specific enhancers and topologically associated domain boundaries of relevant cell types.
Conclusion: Our study provides a resource for identifying and interpreting genomic regulatory DNA variant contributions to human SB genetic predisposition.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613821 | PMC |
http://dx.doi.org/10.1016/j.gimo.2024.101894 | DOI Listing |
Plast Reconstr Surg Glob Open
December 2024
From the Division of Plastic Surgery, Ann and Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL.
Background: Prenatal myelomeningocele (MMC) repair offers significant benefits over traditional postnatal repair, as demonstrated by the Management of Myelomeningocele Study trial. We characterize the current specialist involvement in prenatal and postnatal MMC repair.
Methods: The top 50 US News Children's Hospitals for Neonatology and Neurology/Neurosurgery were queried, resulting in 67 unique hospitals.
BMC Urol
December 2024
Department of Pediatric Surgery, Faculty of Medicine, Istanbul Medeniyet University, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Türkiye, Turkey.
Introduction: Spina bifida is a condition that impacts the development of the neural tube leading to urological and gastrointestinal symptoms. Both systems are influenced together due to their shared innervation and embryological origin. Despite its impact on health and well-being there has been limited research on the relationship between manometry results and urodynamic tests, in this patient population.
View Article and Find Full Text PDFPrenat Diagn
December 2024
Edward B. Singleton Department of Radiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, USA.
J Evid Based Med
December 2024
School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China.
Objective: This study aims to investigate the occurrence of adverse events associated with topiramate by analyzing data from the FDA Adverse Event Reporting System. The goal is to provide a basis for the safe clinical use of topiramate.
Methods: Adverse event data from the FDA Adverse Event Reporting System, from its inception through the first quarter of 2024, were extracted.
Placenta
December 2024
Health Sciences, Carleton University, Ottawa, ON, K1S 5B6, Canada. Electronic address:
Introduction: Spina bifida (SB) remains one of the most common congenital anomalies and associates with significant comorbidities in the fetus, which may, in part, be driven by placental maldevelopment. We hypothesised that placental pathologies would be more prevalent in fetuses with SB compared to fetuses without congenital anomalies.
Methods: Placental pathology and transcriptome were evaluated for fetuses with isolated open SB born preterm (cases; n = 12) and control fetuses without congenital anomalies (n = 22) born at full term (FT) or preterm (PT).
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