ArticleAmerican journal of human genetics2017
Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Arthrogryposis Multiplex Congenita: Comprehensive Review from a Neuromuscular Standpoint.Genes · 2026Review
- Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.Cardiovascular research · 2026Article
- The evolving genetic landscape of neuromuscular fetal akinesias.Journal of neuromuscular diseases · 2025Review
- Integrated TWAS, GWAS, and RNAseq results identify candidate genes associated with reproductive traits in cows.Scientific reports · 2025Article
- Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity.Cell reports · 2024Article
- Anti-LGI4 Antibody Is a Novel Juxtaparanodal Autoantibody for Chronic Inflammatory Demyelinating Polyneuropathy.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Article
- A reverse genetics and genomics approach to gene paralog function and disease: Myokymia and the juxtaparanode.American journal of human genetics · 2022Article
- Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita.Journal of medical genetics · 2022Article
- Natural human knockouts and Mendelian disorders: deep phenotyping in Italian isolates.European journal of human genetics : EJHG · 2021Article
- Schwann cell interactions during the development of the peripheral nervous system.Developmental neurobiology · 2021Review
- Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study.Journal of clinical medicine · 2021Article
- Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.Cellular and molecular life sciences : CMLS · 2019Review
- KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis.American journal of human genetics · 2018Article
Corrections and comments
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Authors and funding
26 authors at 13 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons. Immunolabeling experiments and transmission electron microscopy of the sciatic nerve from one of the affected individuals revealed a lack of myelin. Functional tests using affected individual-derived iPSCs showed that these germline mutations caused aberrant splicing of the endogenous LGI4 transcript and in a cell-based assay impaired the secretion of truncated LGI4 protein. This is consistent with previous studies reporting arthrogryposis in Lgi4-deficient mice due to peripheral hypomyelination. This study adds to the recent reports implicating defective axoglial function as a key cause of AMC.
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