Skip to main content
SpringerLink
Log in
Book cover

Epilepsy Towards the Next Decade pp 35–45Cite as

LGI1 Dysfunction in Inherited and Acquired Epileptic Disorders

  • Chapter
  • First Online:

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

LGI1 is a multifunctional brain protein whose dysfunction is related to several neurologic disorders as diverse as autosomal dominant lateral temporal epilepsy (ADLTE), autoimmune limbic encephalitis (LE), and glioma tumor progression. ADLTE is a genetic focal epilepsy characterized by auditory or aphasic aura and onset in infancy/adolescence, whereas autoimmune LE occurs in adult life and is characterized by amnesia, confusion, and seizures. The complex molecular mechanisms underlying these epileptic conditions are largely unknown. In this chapter, I outline the clinical features, the genetic or autoimmune causes, and a molecular mechanism possibly underlying both ADLTE and autoimmune LE.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Berghuis B, Brilstra EH, Lindhout D et al (2013) Hyperactive behavior in a family with autosomal dominant lateral temporal lobe epilepsy caused by a mutation in the LGI1/epitempin gene. Epilepsy Behav 28:41–46

    Article  CAS  PubMed  Google Scholar 

  • Berkovic SF, Izzillo P, McMahon JM et al (2004) LGI1 mutations in temporal lobe epilepsies. Neurology 62:1115–1119

    Article  CAS  PubMed  Google Scholar 

  • Bisulli F, Tinuper P, Avoni P et al (2004a) Idiopathic partial epilepsy with auditory features (IPEAF): a clinical and genetic study of 53 sporadic cases. Brain 127:1343–1352

    Article  CAS  Google Scholar 

  • Bisulli F, Tinuper P, Scudellaro E et al (2004b) A de novo LGI1 mutation in sporadic partial epilepsy with auditory features. Ann Neurol 56:455–456

    Article  Google Scholar 

  • Brodtkorb E, Michler RP, Gu W et al (2005) Speech-induced aphasic seizures in epilepsy caused by LGI1 mutation. Epilepsia 46:963–966

    Article  PubMed  Google Scholar 

  • Chabrol E, Popescu C, Gourfinkel-An I et al (2007) Two novel epilepsy-linked mutations leading to a loss of function of LGI1. Arch Neurol 64:217–222

    Article  PubMed Central  PubMed  Google Scholar 

  • Chabrol E, Navarro V, Provenzano G et al (2010) Electroclinical characterization of epileptic seizures in leucine-rich, glioma-inactivated 1- deficient mice. Brain 133:2749–2762

    Article  PubMed Central  PubMed  Google Scholar 

  • Chernova OB, Somerville RP, Cowell JK (1998) A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors. Oncogene 17:2873–2881

    Article  CAS  PubMed  Google Scholar 

  • Dalmau J, Gleichman AJ, Hughes EG et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • de Bellescize J, Boutry N, Chabrol E et al (2009) A novel three base-pair LGI1 deletion leading to loss of function in a family with autosomal dominant lateral temporal epilepsy and migraine-like episodes. Epilepsy Res 85:118–122

    Article  CAS  PubMed  Google Scholar 

  • Di Bonaventura C, Carni M, Diani E et al (2009) Drug resistant ADLTE and recurrent partial status epilepticus with dysphasic features in a family with a novel LGI1 mutation: electroclinical, genetic, and EEG/fMRI findings. Epilepsia 50:2481–2486

    Article  PubMed  Google Scholar 

  • Di Bonaventura C, Operto FF, Busolin G et al (2011) Low penetrance and effect on protein secretion of LGI1 mutations causing autosomal dominant lateral temporal epilepsy. Epilepsia 52:1258–1264

    Article  CAS  PubMed  Google Scholar 

  • Fertig E, Lincoln A, Martinuzzi A et al (2003) Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features. Neurology 60:1687–1690

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fanciulli M, Santulli L, Errichiello L et al (2012) LGI1 microdeletion in autosomal dominant lateral temporal epilepsy. Neurology 78:1299–1303

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fukata Y, Adesnik H, Iwanaga T et al (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science 313:1792–1795

    Article  CAS  PubMed  Google Scholar 

  • Fukata Y, Lovero KL, Iwanaga T et al (2010) Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci U S A 107:3799–3804

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gable MS, Gavali S, Radner A et al (2009) Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis 28:1421–1429

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gu W, Brodtkorb E, Steinlein OK (2002) LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures. Ann Neurol 52:364–367

    Article  CAS  PubMed  Google Scholar 

  • Hart IK, Waters C, Vincent A et al (1997) Autoantibodies detected to expressed Kþ channels are implicated in neuromyotonia. Ann Neurol 41:238–246

    Article  CAS  PubMed  Google Scholar 

  • Hart IK, Maddison P, Newsom-Davis J et al (2002) Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 125:1887–1895

    Article  PubMed  Google Scholar 

  • Hedera P, Abou-Khalil B, Crunk AE et al (2004) Autosomal dominant lateral temporal epilepsy: two families with novel mutations in the LGI1 gene. Epilepsia 45:218–222

    Article  CAS  PubMed  Google Scholar 

  • Heiman GA, Kamberakis K, Gill R et al (2010) Evaluation of depression risk in LGI1 mutation carriers. Epilepsia 51:1685–1690

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ho YY, Ionita-Laza I, Ottman R (2012) Domain-dependent clustering and genotype-phenotype analysis of LGI1 mutations in ADPEAF. Neurology 78:563–568

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Irani SR, Buckley C, Vincent A et al (2008) Immunotherapy-responsive seizure-like episodes with potassium channel antibodies. Neurology 71:1647–1648

    Article  CAS  PubMed  Google Scholar 

  • Irani SR, Alexander S, Waters P et al (2010) Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 133:2734–2748

    Article  PubMed Central  PubMed  Google Scholar 

  • Irani SR, Michell AW, Lang B et al (2011) Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 69:892–900

    Article  PubMed  Google Scholar 

  • Irani SR, Pettingill P, Kleopa KA et al (2012) Morvan syndrome: Clinical and serological observations in 29 cases. Ann Neurol 72:241–255

    Article  PubMed  Google Scholar 

  • Irani SR, Charlotte JS, Schott JM et al (2013) Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain 136:3151–3162

    Article  PubMed  Google Scholar 

  • Kalachikov S, Evgrafov O, Ross B et al (2002) Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet 30:335–341

    Article  PubMed Central  PubMed  Google Scholar 

  • Kawamata J, Ikeda A, Fujita Y et al (2010) Mutations in LGI1 gene in Japanese families with autosomal dominant lateral temporal lobe epilepsy: the first report from Asian families. Epilepsia 51:690–693

    Article  CAS  PubMed  Google Scholar 

  • Kobe B, Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11:725–732

    Article  CAS  PubMed  Google Scholar 

  • Kunapuli P, Chitta KS, Cowell JK (2003) Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene. Oncogene 22:3985–3991

    Article  CAS  PubMed  Google Scholar 

  • Kunapuli P, Kasyapa CS, Hawthorn L et al (2004) LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway. J Biol Chem 279:23151–23157

    Article  CAS  PubMed  Google Scholar 

  • Leonardi E, Andreazza S, Vanin S et al (2011) A computational model of the LGI1 protein suggests a common binding site for ADAM proteins. Plos One 6:e18142

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lai M, Huijbers MGM, Lancaster E et al (2010) Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 9:776–785

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee MK, Kim SW, Lee JH et al (2014) A Newly discovery of LGI1 mutation in a Korean family with autosomal dominant lateral temporal lobe epilepsy. Seizure 23:69–73

    Article  PubMed  Google Scholar 

  • Michelucci R, Poza JJ, Sofia V et al (2003) Autosomal dominant lateral temporal epilepsy: clinical spectrum, new epitempin mutations, and genetic heterogeneity in seven European families. Epilepsia 44:1289–1297

    Article  CAS  PubMed  Google Scholar 

  • Michelucci R, Mecarelli O, Bovo G et al (2007) A de novo LGI1 mutation causing idiopathic partial epilepsy with telephone-induced seizures. Neurology 68:2150–2151

    Article  CAS  PubMed  Google Scholar 

  • Michelucci R, Pasini E, Nobile C (2009) Lateral temporal lobe epilepsies: clinical and genetic features. Epilepsia 50(Suppl 5):52–54

    Article  CAS  PubMed  Google Scholar 

  • Michelucci R, Pasini E, Malacrida S et al (2013) Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without LGI1 mutations. Epilepsia 54:1288–1297

    Article  CAS  PubMed  Google Scholar 

  • Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S et al (2002) Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum Mol Genet 11:1119–1128

    Article  CAS  PubMed  Google Scholar 

  • Nobile C, Michelucci R, Andreazza S et al (2009) LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy. Hum Mutat 30:530–536

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa T, Fukata Y, Yamasaki M et al (2013) Autoantibodies to Epilepsy-Related LGI1 in Limbic Encephalitis Neutralize LGI1-ADAM22 Interaction and Reduce Synaptic AMPA Receptors. J Neurosci 33:18161–18174

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Owuor K, Harel NY, Englot DJ et al (2009) LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. Mol Cell Neurosci 42:448–457

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ottman R, Risch N, Hauser WA et al (1995) Localization of a gene for partial epilepsy to chromosome 10q. Nat Genet 10:56–60

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ottman R, Winawer MR, Kalachikov S et al (2004) LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 62:1120–1126

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Paoli M (2001) Protein folds propelled by diversity. Prog Biophys Molec Biol 76:103–130

    Article  CAS  Google Scholar 

  • Piepoli T, Jakupoglu C, Gu W et al (2006) Expression studies in gliomas and glial cells do not support a tumor suppressor role for LGI1. Neuro Oncol 8:96–108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pisano T, Marini C, Brovedani P et al (2005) Abnormal phonologic processing in familial lateral temporal lobe epilepsy due to a new LGI1 mutation. Epilepsia 46:118–123

    Article  CAS  PubMed  Google Scholar 

  • Pizzuti A, Flex E, Di Bonaventura C et al (2003) Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism. Ann Neurol 53:396–399. Erratum in. Ann Neurol 2003;54:137

    Article  Google Scholar 

  • Rosanoff MJ, Ottman R (2008) Penetrance of LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 71:567–571

    Article  PubMed Central  PubMed  Google Scholar 

  • Sadleir LG, Agher D, Chabrol E et al (2013) Seizure semiology in autosomal dominant epilepsy with auditory features, due to novel LGI1 mutations. Epilepsy Res 107:311–317

    Article  CAS  PubMed  Google Scholar 

  • Sagane K, Hayakawa K, Kaj J et al (2005) Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice. BMC Neurosci 6:33

    Article  CAS  PubMed  Google Scholar 

  • Schulte U, Thumfart JO, Klocker N et al (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic kv1 channels and inhibits inactivation by Kvbeta1. Neuron 49:697–706

    Article  CAS  PubMed  Google Scholar 

  • Senechal KR, Thaller C, Noebels JL (2005) ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor protein linked to epilepsy. Hum Mol Genet 14:1613–1620

    Article  CAS  PubMed  Google Scholar 

  • Somerville RP, Chernova O, Liu S et al (2000) Identification of the promoter, genomic structure, and mouse ortholog of LGI1. Mamm Genome 11:622–627

    Article  CAS  PubMed  Google Scholar 

  • Staub E, Perez-Tur J, Siebert R et al (2002) The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders. Trends Biochem Sci 27:441–444

    Article  CAS  PubMed  Google Scholar 

  • Striano P, de Falco A, Diani E et al (2008) A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy. Arch Neurol 65:939–942

    PubMed  Google Scholar 

  • Striano P, Busolin G, Santulli L et al (2011) Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation. Neurology 76:1173–1176

    Article  CAS  PubMed  Google Scholar 

  • Tan KM, Lennon VA, Klein CJ et al (2008) Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 70:1883–1890

    Article  CAS  PubMed  Google Scholar 

  • Tessa C, Michelucci R, Nobile C et al (2007) Structural anomaly of left lateral temporal lobe in epilepsy due to mutated LGI1. Neurology 69:1298–1300

    Article  CAS  PubMed  Google Scholar 

  • Vincent A, Buckley C, Schott JM et al (2004) Potassium channel antibodyassociated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 127:701–712

    Article  PubMed  Google Scholar 

  • Vincent A, Bien CG, Irani SR et al (2011) Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol 10:759–772

    Article  CAS  PubMed  Google Scholar 

  • Warmolts JR, Mendell JR (1980) Neurotonia: impulse-induced repetitive discharges in motor nerves in peripheral neuropathy. Ann Neurol 7:245–250

    Article  CAS  PubMed  Google Scholar 

  • Yu YE, Wen L, Silva J et al (2010) Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability. Hum Mol Genet 19:1702–1711

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou YD, Lee S, Jin Z et al (2009) Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy. Nat Med 15:1208–1214

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CNR-Neuroscience Institute, Padova, Italy

    Carlo Nobile

Authors
  1. Carlo Nobile
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlo Nobile .

Editor information

Editors and Affiliations

  1. DINOGMI, University of Genoa, Genova, Genova, Italy

    Pasquale Striano

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Nobile, C. (2015). LGI1 Dysfunction in Inherited and Acquired Epileptic Disorders. In: Striano, P. (eds) Epilepsy Towards the Next Decade. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-12283-0_3

Download citation

Publish with us

Policies and ethics

Search

Navigation