ArticleBMC medical genomics2018
Genetic analysis of Wnt/PCP genes in neural tube defects.
Article in BMC medical genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 59 citations in OpenAlex.
- Whole exome sequencing uncovers novel genetic insights into Tethered cord syndrome.Molecular genetics and genomics : MGG · 2026Article
- Unravelıng non-canonıcal Wnt sıgnalıng ın neural development and dısorders: a revıew of Wnt/PCP and Wnt/caMolecular biology reports · 2026Review
- Uncovering the Genetic Landscape of Spinal Dysraphism: A Retrospective Analysis of 150 Fetal Cases.Prenatal diagnosis · 2026Article
- Quantitative live imaging reveals PRICKLE1 controls junctional neural tube morphogenesis independent of Planar Cell Polarity.Nature communications · 2026Article
- The expanding roles of adhesion GPCRs in neural circuit assembly.Molecules and cells · 2026Review
- Review
- Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling.Developmental biology · 2025Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Fold-and-fuse neurulation in zebrafish requires vangl2.Developmental biology · 2025Article
- Human organoids potentially boost research into environmental factors of neural tube defects.Reproductive toxicology (Elmsford, N.Y.) · 2025Review
- Structural basis for regulation of CELSR1 by a compact module in its extracellular region.Nature communications · 2025Article
- Integrative Analysis of Key Signalling Pathways in Neural Tube Defects: From Molecular Mechanisms to Therapeutic Strategies.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2025Review
- Parental arsenic exposure and tissue-specific DNA methylation in Bangladeshi infants with spina bifida.Epigenetics · 2024Article
- Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects.Human genetics · 2024Article
- Genome-wide analysis of spina bifida risk variants in a case-control study from Bangladesh.Birth defects research · 2024Article
- Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.NPJ genomic medicine · 2024Article
- Evaluating Computer Vision, Large Language, and Genome-Wide Association Models in a Limited Sized Patient Cohort for Pre-Operative Risk Stratification in Adult Spinal Deformity Surgery.Journal of clinical medicine · 2024Article
- Identification and Functional Analysis of Rare HECTD1 Missense Variants in Human Neural Tube Defects.Research square · 2024Article
- Review
- Loss-of-Function of p21-Activated Kinase 2 Links BMP Signaling to Neural Tube Patterning Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMouse homozygous mutants in Wnt/planar cell polarity (PCP) pathway genes have been shown to cause neural tube defects (NTDs) through the disruption of normal morphogenetic processes critical to neural tube closure (NTC). Knockout mice that are heterozygotes of single PCP genes likely fail to produce NTD phenotypes, yet damaging variants detected in human NTDs are almost always heterozygous, suggesting that other deleterious interacting variants are likely to be present. Nonetheless, the Wnt/PCP pathway remains a genetic hotspot. Addressing these issues is essential for understanding the genetic etiology of human NTDs.
methodsWe performed targeted next-generation sequencing (NGS) on 30 NTD-predisposing Wnt/PCP pathway genes in 184 Chinese NTD cases. We subsequently replicated our findings for the CELSR1 gene in an independent cohort of 292 Caucasian NTD samples from the USA. Functional validations were confirmed using in vitro assays.
resultsCELSR1, CELSR2 and CELSR3 genes were significantly clustered with rare driver coding mutations (q-value< 0.05) demonstrated by OncodriveCLUST. During the validation stage, the number of rare loss of function (LoF) variants in CELSR1 was significantly enriched in NTDs compared with the LoF counts in the ExAC database (p < 0.001). Functional studies indicated compound heterozygote variants of CELSR2 p.Thr2026Met and DVL3 p.Asp403Asn result in down regulation of PCP signals.
conclusionsThese data indicate rare damaging variants of the CELSR genes, identified in ~ 14% of NTD cases, are expected to be driver genes in the Wnt/PCP pathway. Compound damaging variants of CELSR genes and other Wnt/PCP genes, which were observed in 3.3% of the studied NTD cohort, are also expected to amplify these effects at the pathway level.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.