ArticleBrain : a journal of neurology2022
Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- CRISPR/Cas9 loss-of-function screen in a neuronal model of AP-4 deficiency identifies ATG9A trafficking modulators.JCI insight · 2026Article
- Psychiatric symptoms as clinical warning signals of adult anti-LGI-1 encephalitis: an observational cohort study.BMC psychiatry · 2026Observational
- Biallelic LGI1 and ADAM23 variants cause hippocampal epileptic encephalopathy via the LGI1-ADAM22/23 pathway.Brain : a journal of neurology · 2025Article
- A hierarchy of PDZ domain scaffolding proteins clusters the Kv1 KScience advances · 2025Article
- Patient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models.Brain, behavior, and immunity · 2025Article
- Whole Exome Sequencing Identifies Novel Homozygous LGI1 Variant Mimicking ADAM22-Related Pathologies in a Moroccan Family.BMJ neurology open · 2025Article
- Evaluation of the etiology of epilepsy and/or developmental delay in children via next-generation sequencing: a single-center experience.Frontiers in pediatrics · 2025Article
- Developmental and epileptic encephalopathies.Nature reviews. Disease primers · 2024Review
- Celebrating the Birthday of AMPA Receptor Nanodomains: Illuminating the Nanoscale Organization of Excitatory Synapses with 10 Nanocandles.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications.Nature communications · 2024Article
- Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity.Cell reports · 2024Article
- Inactive metallopeptidase homologs: the secret lives of pseudopeptidases.Frontiers in molecular biosciences · 2024Review
- LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period.The Journal of cell biology · 2023Article
- A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating KCell & bioscience · 2023Article
- The versatile roles of ADAM8 in cancer cell migration, mechanics, and extracellular matrix remodeling.Frontiers in cell and developmental biology · 2023Review
- Article
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Authors and funding
48 authors at 20 institutions in 16 countries.
Funding
Abstract
Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harbouring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20) and delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: (i) defective cell membrane expression; (ii) impaired LGI1-binding; and/or (iii) impaired interaction with the postsynaptic density protein PSD-95. We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics.
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