Trial reportHuman molecular genetics2015
Increased burden of de novo predicted deleterious variants in complex congenital diaphragmatic hernia.
Trial report in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00950118 (Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science), which is not on this map. Cited by 46 papers.
What it found
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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.
Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science
Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- Mechanical compression causes lung hypoplasia in congenital diaphragmatic hernia with GATA4 genetic variants.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Novel variants inExperimental and therapeutic medicine · 2026Article
- Deconvolution of DNA methylation data reveals cell type-specific epigenomic signatures in endometriosis and eutopic endometrium.Molecular human reproduction · 2026Article
- STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling.iScience · 2025Article
- A novelGlobal medical genetics · 2025Article
- Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants.American journal of human genetics · 2024Article
- The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later.Pediatric research · 2024Review
- Rescuing lung development through embryonic inhibition of histone acetylation.Science translational medicine · 2024Article
- PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.American journal of human genetics · 2023Article
- Fetal lung hypoxia and energetic cell failure in the nitrofen-induced congenital diaphragmatic hernia rat model.Pediatric surgery international · 2023Article
- The role of genes and environment in the etiology of congenital diaphragmatic hernias.Current topics in developmental biology · 2023Review
- Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.American journal of medical genetics. Part A · 2022Article
- Article
- Congenital diaphragmatic hernia.Nature reviews. Disease primers · 2022Review
- Review
- Inhibition of mitochondrial LonP1 protease by allosteric blockade of ATP binding and hydrolysis via CDDO and its derivatives.The Journal of biological chemistry · 2022Article
- Underlying genetic etiologies of congenital diaphragmatic hernia.Prenatal diagnosis · 2022Review
- Genetically Modified Mouse Models of Congenital Diaphragmatic Hernia: Opportunities and Limitations for Studying Altered Lung Development.Frontiers in pediatrics · 2022Review
- Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene.American journal of human genetics · 2021Article
- Expanding the known phenotype of Mullegama-Klein-Martinez syndrome in male patients.Human genome variation · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Congenital diaphragmatic hernia (CDH) is a serious birth defect that accounts for 8% of all major birth anomalies. Approximately 40% of cases occur in association with other anomalies. As sporadic complex CDH likely has a significant impact on reproductive fitness, we hypothesized that de novo variants would account for the etiology in a significant fraction of cases. We performed exome sequencing in 39 CDH trios and compared the frequency of de novo variants with 787 unaffected controls from the Simons Simplex Collection. We found no significant difference in overall frequency of de novo variants between cases and controls. However, among genes that are highly expressed during diaphragm development, there was a significant burden of likely gene disrupting (LGD) and predicted deleterious missense variants in cases (fold enrichment = 3.2, P-value = 0.003), and these genes are more likely to be haploinsufficient (P-value = 0.01) than the ones with benign missense or synonymous de novo variants in cases. After accounting for the frequency of de novo variants in the control population, we estimate that 15% of sporadic complex CDH patients are attributable to de novo LGD or deleterious missense variants. We identified several genes with predicted deleterious de novo variants that fall into common categories of genes related to transcription factors and cell migration that we believe are related to the pathogenesis of CDH. These data provide supportive evidence for novel genes in the pathogenesis of CDH associated with other anomalies and suggest that de novo variants play a significant role in complex CDH cases.
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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.