ArticleHuman molecular genetics2013
Deficiency of FRAS1-related extracellular matrix 1 (FREM1) causes congenital diaphragmatic hernia in humans and mice.
Article in Human molecular genetics, 2013. 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 25 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
25 citing papers in PubMed, 44 citations in OpenAlex.
- WNT4 deficiency impacts heart, diaphragm, and palate development: Insights from human genetics, machine learning, and mouse models.Developmental biology · 2026Article
- Contribution of omics to the pathophysiology of diaphragmatic hernias: a narrative review.European journal of pediatrics · 2025Review
- Two novel mutations within FREM1 gene in patients with bifid nose.BMC pediatrics · 2023Article
- Frem1 activity is regulated by Sonic hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Evidence for an association between Coffin-Siris syndrome and congenital diaphragmatic hernia.American journal of medical genetics. Part A · 2022Review
- Clinical exome sequencing data reveal high diagnostic yields for congenital diaphragmatic hernia plus (CDH+) and new phenotypic expansions involving CDH.Journal of medical genetics · 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
- The Potential Role of FREM1 and Its Isoform TILRR in HIV-1 Acquisition through Mediating Inflammation.International journal of molecular sciences · 2021Review
- Unraveling the Genetics of Congenital Diaphragmatic Hernia: An Ongoing Challenge.Frontiers in pediatrics · 2021Review
- Transgenic animal models of congenital diaphragmatic hernia: a comprehensive overview of candidate genes and signaling pathways.Pediatric surgery international · 2020Review
- An omic approach to congenital diaphragmatic hernia: a pilot study of genomic, microRNA, and metabolomic profiling.Journal of perinatology : official journal of the California Perinatal Association · 2020Article
- The influence of genetics in congenital diaphragmatic hernia.Seminars in perinatology · 2020Review
- Article
- Toll-like Interleukin 1 Receptor Regulator Is an Important Modulator of Inflammation Responsive Genes.Frontiers in immunology · 2019Article
- RERE deficiency leads to decreased expression of GATA4 and the development of ventricular septal defects.Disease models & mechanisms · 2018Article
- The role of FREM2 and FRAS1 in the development of congenital diaphragmatic hernia.Human molecular genetics · 2018Article
- Congenital diaphragmatic hernias: from genes to mechanisms to therapies.Disease models & mechanisms · 2017Review
- Decreased Desmin expression in the developing diaphragm of the nitrofen-induced congenital diaphragmatic hernia rat model.Pediatric surgery international · 2016Article
- Mesenchymal expression of the FRAS1/FREM2 gene unit is decreased in the developing fetal diaphragm of nitrofen-induced congenital diaphragmatic hernia.Pediatric surgery international · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Congenital diaphragmatic hernia (CDH) is a common life-threatening birth defect. Recessive mutations in the FRAS1-related extracellular matrix 1 (FREM1) gene have been shown to cause bifid nose with or without anorectal and renal anomalies (BNAR) syndrome and Manitoba oculotrichoanal (MOTA) syndrome, but have not been previously implicated in the development of CDH. We have identified a female child with an isolated left-sided posterolateral CDH covered by a membranous sac who had no features suggestive of BNAR or MOTA syndromes. This child carries a maternally-inherited ~86 kb FREM1 deletion that affects the expression of FREM1's full-length transcripts and a paternally-inherited splice site mutation that causes activation of a cryptic splice site, leading to a shift in the reading frame and premature termination of all forms of the FREM1 protein. This suggests that recessive FREM1 mutations can cause isolated CDH in humans. Further evidence for the role of FREM1 in the development of CDH comes from an N-ethyl-N-nitrosourea -derived mouse strain, eyes2, which has a homozygous truncating mutation in Frem1. Frem1(eyes2) mice have eye defects, renal agenesis and develop retrosternal diaphragmatic hernias which are covered by a membranous sac. We confirmed that Frem1 is expressed in the anterior portion of the developing diaphragm and found that Frem1(eyes2) embryos had decreased levels of cell proliferation in their developing diaphragms when compared to wild-type embryos. We conclude that FREM1 plays a critical role in the development of the diaphragm and that FREM1 deficiency can cause CDH in both humans and mice.
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.