ArticleAmerican journal of human genetics2010
Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren's disease.Nature communications · 2024Pooled it
- Defining the role of common variation in the genomic and biological architecture of adult human height.Nature genetics · 2014Pooled it
- Integrated multi-omics and single-cell analyses identify metabolic heterogeneity and therapeutic vulnerabilities in medullary thyroid cancer.British journal of cancer · 2026Article
- Dysregulation of the Cant1/β-Catenin/TCF4-CHSY1 Axis Underpins Impaired ECM Biosynthesis in Skeletal Disorders.Research (Washington, D.C.) · 2026Article
- Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate.Journal of human genetics · 2025Review
- Chondroitin sulfate regulates proliferation of Drosophila intestinal stem cells.PLoS genetics · 2025Article
- Self-Assembled Nanoparticles with Well-Defined Oligosaccharide Promote Osteogenesis by Regulating Golgi Stress Response.Advanced healthcare materials · 2025Article
- Epigenome-850K-wide profiling reveals peripheral blood differential methylation in term low birth weight.Epigenomics · 2024Article
- Chondroitin sulfate is required for follicle epithelial integrity and organ shape maintenance in Drosophila.Development (Cambridge, England) · 2023Article
- Chemistry and Function of Glycosaminoglycans in the Nervous System.Advances in neurobiology · 2023Review
- Chondroitin/dermatan sulfate glycosyltransferase genes are essential for craniofacial development.PLoS genetics · 2022Article
- Roles of Chondroitin Sulfate Proteoglycans as Regulators of Skeletal Development.Frontiers in cell and developmental biology · 2022Review
- Notch signaling: Its essential roles in bone and craniofacial development.Genes & diseases · 2021Review
- Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish.Theranostics · 2021Article
- An Overview ofFrontiers in cell and developmental biology · 2021Review
- Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis.Frontiers in genetics · 2021Review
- Chondrodysplasias With Multiple Dislocations Caused by Defects in Glycosaminoglycan Synthesis.Frontiers in genetics · 2021Review
- Generation and Application of the ZebrafishBiomolecules · 2020Article
- Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.Nature communications · 2020Article
- Loss of Chondroitin Sulfate Modification Causes Inflammation and Neurodegeneration inGenetics · 2020Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We delineated a syndromic recessive preaxial brachydactyly with partial duplication of proximal phalanges to 16.8 Mb over 4 chromosomes. High-throughput sequencing of all 177 candidate genes detected a truncating frameshift mutation in the gene CHSY1 encoding a chondroitin synthase with a Fringe domain. CHSY1 was secreted from patients' fibroblasts and was required for synthesis of chondroitin sulfate moieties. Noticeably, its absence triggered massive production of JAG1 and subsequent NOTCH activation, which could only be reversed with a wild-type but not a Fringe catalytically dead CHSY1 construct. In vitro, depletion of CHSY1 by RNAi knockdown resulted in enhanced osteogenesis in fetal osteoblasts and remarkable upregulation of JAG2 in glioblastoma cells. In vivo, chsy1 knockdown in zebrafish embryos partially phenocopied the human disorder; it increased NOTCH output and impaired skeletal, pectoral-fin, and retinal development. We conclude that CHSY1 is a secreted FRINGE enzyme required for adjustment of NOTCH signaling throughout human and fish embryogenesis and particularly during limb patterning.
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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.