ArticleHuman mutation2022
CIC missense variants contribute to susceptibility for spina bifida.
Article in Human mutation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Folic Acid Metabolism and Its Impact on Neurogenesis: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- Decoding structural birth defects through genomic landscapes: Innovative frameworks for diagnosis (Review).International journal of molecular medicine · 2026Review
- Spina bifida as a multifactorial birth defect: Risk factors and genetic underpinnings.Pediatric discovery · 2025Review
- Genome-wide analysis of spina bifida risk variants in a case-control study from Bangladesh.Birth defects research · 2024Article
- Bayesian polygenic risk estimation approach to nuclear families with discordant sib-pairs for myelomeningocele.PloS one · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Neural tube defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to the cerebral folate deficiency syndrome by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased risk for NTDs by depressing embryonic folate concentrations. In this study, we examined CIC variants from whole-genome sequencing (WGS) data of 140 isolated spina bifida cases and identified eight missense variants of CIC gene. We tested the pathogenicity of the observed variants through multiple in vitro experiments. We determined that CIC variants decreased the FOLR1 protein level and planar cell polarity (PCP) pathway signaling in a human cell line (HeLa). In a murine cell line (NIH3T3), CIC loss of function variants downregulated PCP signaling. Taken together, this study provides evidence supporting CIC as a risk gene for human NTD.
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