Evidence map›Paper›PMID 27066583›Full record

ArticleNeurology. Genetics2016

Dysfunctional ADAM22 implicated in progressive encephalopathy with cortical atrophy and epilepsy.

Mikko Muona, Yuko Fukata, Anna-Kaisa Anttonen, Anni Laari, Aarno Palotie, Helena Pihko, Tuula Lönnqvist, Leena Valanne, Mirja Somer, Masaki Fukata and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology. Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 36 citations in OpenAlex.

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  6. Brain communications · 2023
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  10. LGI1-ADAM22-MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention.Proceedings of the National Academy of Sciences of the United States of America · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Mikko MuonaInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Yuko FukataInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Anna-Kaisa AnttonenInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Anni LaariInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Aarno PalotieInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Helena PihkoInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Tuula LönnqvistInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Leena ValanneInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Mirja SomerInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Masaki FukataInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
Anna-Elina LehesjokiInstitute for Molecular Medicine Finland (M.M., A.P.), Neuroscience Center (M.M., A.L., A.-E.L.), and Research Programs Unit, Molecular Neurology (M.M., A.-K.A., A.L., A.-E.L.), University of Helsinki, Finland; Folkhälsan Institute of Genetics (M.M., A.-K.A., A.L., A.-E.L.), Helsinki, Finland; Division of Membrane Physiology (Y.F., M.F.), Department of Cell Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan; Department of Physiological Sciences (Y.F., M.F.), School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan; Medical and Clinical Genetics (A.-K.A.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Analytic and Translational Genetics Unit (A.P.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics (A.P.) and Stanley Center for Psychiatric Research (A.P.), Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; Program in Genetics and Genomics (A.P.), Biological and Biomedical Sciences, Harvard Medical School, Boston, MA; Wellcome Trust Sanger Institute (A.P.), Wellcome Trust Genome Campus, Hinxton, United Kingdom; Psychiatric & Neurodevelopmental Genetics Unit (A.P.), Department of Psychiatry, and Department of Neurology (A.P.), Massachusetts General Hospital, Boston, MA; Department of Pediatric Neurology (H.P., T.L.), Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Radiology (L.V.), HUS Medical Imaging Center, Helsinki, Finland; and Family Federation of Finland (M.S.), Helsinki, Finland.
MACOM (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo identify the molecular genetic basis of a syndrome characterized by rapidly progressing cerebral atrophy, intractable seizures, and intellectual disability.

methodsWe performed exome sequencing in the proband and whole-genome single nucleotide polymorphism genotyping (copy number variant analysis) in the proband-parent trio. We used heterologous expression systems to study the functional consequences of identified mutations.

resultsThe search for potentially deleterious recessive or de novo variants yielded compound heterozygous missense (c.1202G>A, p.Cys401Tyr) and frameshift deletion (c.2396delG, p.Ser799IlefsTer96) mutations in ADAM22, which encodes a postsynaptic receptor for LGI1. The deleterious effect of the mutations was observed in cell surface binding and immunoprecipitation assays, which revealed that both mutant proteins failed to bind to LGI1. Furthermore, immunoprecipitation assays showed that the frameshift mutant ADAM22 also did not bind to the postsynaptic scaffolding protein PSD-95.

conclusionsThe mutations identified abolish the LGI1-ADAM22 ligand-receptor complex and are thus a likely primary cause of the proband's epilepsy syndrome, which is characterized by unusually rapidly progressing cortical atrophy starting at 3-4 months of age. These findings are in line with the implicated role of the LGI1-ADAM22 complex as a key player in nervous system development, specifically in functional maturation of postnatal synapses. Because the frameshift mutation affects an alternatively spliced exon with highest expression in postnatal brain, the combined effect of the mutations is likely to be hypomorphic rather than complete loss of function. This is compatible with the longer survival of the patient compared to Lgi1 (-/-) and Adam22 (-/-) mice, which develop lethal seizures during the first postnatal weeks.

Identifiers

PMID27066583
PMCPMC4817901
OpenAlexW2338785315

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