ArticleAmerican journal of human genetics2015
Mutations of GPR126 are responsible for severe arthrogryposis multiplex congenita.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 119 citations in OpenAlex.
- Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin.The Journal of clinical investigation · 2016Trial
- Arthrogryposis Multiplex Congenita: Comprehensive Review from a Neuromuscular Standpoint.Genes · 2026Review
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Extra-helical allosteric binding site of apomorphine in ADGRG6.Cell discovery · 2026Article
- The far extracellular CUB domain of the adhesion GPCR ADGRG6/GPR126 is a key regulator of receptor signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- The evolving genetic landscape of neuromuscular fetal akinesias.Journal of neuromuscular diseases · 2025Review
- Exploring the presence of the GPR126 single nucleotide polymorphism (rs536714306) in periodontal patients of European ancestry.BMC research notes · 2025Article
- Domain-specific N-glycosylation of the adhesion G-protein-coupled receptor ADGRG6 N-terminal fragment regulates trafficking, proteolytic processing, and signaling.Molecular biology of the cell · 2025Article
- Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease.Genes & diseases · 2025Review
- Transcriptional Changes Associated with Amyoplasia.International journal of molecular sciences · 2024Article
- A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry.Nature communications · 2024Article
- GPR126 is a specifier of blood-brain barrier formation in the mouse central nervous system.The Journal of clinical investigation · 2024Article
- Peripheral Nervous System (PNS) Myelin Diseases.Cold Spring Harbor perspectives in biology · 2024Review
- Placental transcriptomic signatures of prenatal and preconceptional maternal stress.Molecular psychiatry · 2024Article
- Novel PIP5K1C variant identified in a Chinese pedigree with lethal congenital contractural syndrome 3.BMC pediatrics · 2024Article
- The Schwann cell-specific G-protein Gαo (Gnao1) is a cell-intrinsic controller contributing to the regulation of myelination in peripheral nerve system.Acta neuropathologica communications · 2024Article
- Analysis of GPR126 polymorphisms and their relationship with scoliosis in Marfan syndrome and Marfan-like syndrome in Mexican patients.Biomolecules & biomedicine · 2023Article
- A screen of pharmacologically active compounds to identify modulators of the Adgrg6/Gpr126 signalling pathway in zebrafish embryos.Basic & clinical pharmacology & toxicology · 2023Article
- Noncoding SNP at rs1663689 represses ADGRG6 via interchromosomal interaction and reduces lung cancer progression.EMBO reports · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 11 institutions in 4 countries.
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Abstract
Arthrogryposis multiplex congenita is defined by the presence of contractures across two or more major joints and results from reduced or absent fetal movement. Here, we present three consanguineous families affected by lethal arthrogryposis multiplex congenita. By whole-exome or targeted exome sequencing, it was shown that the probands each harbored a different homozygous mutation (one missense, one nonsense, and one frameshift mutation) in GPR126. GPR126 encodes G-protein-coupled receptor 126, which has been shown to be essential for myelination of axons in the peripheral nervous system in fish and mice. A previous study reported that Gpr126(-/-) mice have a lethal arthrogryposis phenotype. We have shown that the peripheral nerves in affected individuals from one family lack myelin basic protein, suggesting that this disease in affected individuals is due to defective myelination of the peripheral axons during fetal development. Previous work has suggested that autoproteolytic cleavage is important for activating GPR126 signaling, and our biochemical assays indicated that the missense substitution (p.Val769Glu [c.2306T>A]) impairs autoproteolytic cleavage of GPR126. Our data indicate that GPR126 is critical for myelination of peripheral nerves in humans. This study adds to the literature implicating defective axoglial function as a key cause of severe arthrogryposis multiplex congenita and suggests that GPR126 mutations should be investigated in individuals affected by this disorder.
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