Top

Published in:

01-05-2005 | Review Article

LGI1: a gene involved in epileptogenesis and glioma progression?

Authors: W. Gu, E. Brodtkorb, T. Piepoli, G. Finocchiaro, O. K. Steinlein

Published in: Neurogenetics | Issue 2/2005

Abstract

The leucine-rich, glioma inactivated gene 1 (LGI1) gene on human chromosome 10q24 was first identified as a candidate tumor suppressor gene for glioma. Surprisingly, mutations in LGI1 were also shown to cause an idiopathic epilepsy syndrome, autosomal dominant lateral temporal lobe epilepsy (ADLTE). LGI1 is one of the only two currently known non-ion channel genes whose mutations cause idiopathic epilepsy in humans. In this review we summarize the current data on structure and function of the LGI1 protein and discuss clinical aspects of ADLTE and their correlation with LGI1. We also propose that the evidence supporting the tumor suppressor role of LGI1 in malignant gliomas is weak and that further work is necessary to establish LGI1 role in glial cells.

Kalachikov S, Evgrafov O, Ross B, Winawer M, Barker-Cummings C, Martinelli Boneschi F, Choi C, Morozov P, Das K, Teplitskaya E, Yu A, Cayanis E, Penchaszadeh G, Kottmann AH, Pedley TA, Hauser WA, Ottman R, Gilliam TC (2002) Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat Genet 30:335–341PubMed

Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S, Saenz A, Poza JJ, Galan J, Gesk S, Sarafidou T, Mautner VF, Binelli S, Staub E, Hinzmann B, French L, Prud’homme JF, Passarelli D, Scannapieco P, Tassinari CA, Avanzini G, Marti-Masso JF, Kluwe L, Deloukas P, Moschonas NK, Michelucci R, Siebert R, Nobile C, Perez-Tur J, Lopez de Munain A (2002) Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy. Hum Mol Genet 11:1119–1128

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

Ottman R, Risch N, Hauser WA, Pedley TA, Lee JH, Barker-Cummings C, Lustenberger A, Nagle KJ, Lee KS, Scheuer ML (1995) Localization of a gene for partial epilepsy to chromosome 10q. Nat Genet 10:56–60

Ottman R, Winawer MR, Kalachikov S, Barker-Cummings C, Gilliam TC, Pedley TA, Hauser WA (2004) LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 62:1120–1126

Brodtkorb E, Gu W, Nakken KO, Fischer C, Steinlein OK (2002) Familial temporal lobe epilepsy with aphasic seizures and linkage to chromosome 10q22–q24. Epilepsia 43:228–235CrossRefPubMed

Pizzuti A, Flex E, Di Bonaventura C, Dottorini T, Egeo G, Manfredi M, Dallapiccola B, Giallonardo AT (2003) Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism. Ann Neurol 53:396–399

Pizzuti A, Giallonardo AT (2003) Erratum. Ann Neurol 54:137

Michelucci R, Poza JJ, Sofia V, de Feo MR, Binelli S, Bisulli F, Scudellaro E, Simionati B, Zimbello R, D’Orsi G, Passarelli D, Avoni P, Avanzini G, Tinuper P, Biondi R, Valle G, Mautner VF, Stephani U, Tassinari CA, Moschonas NK, Siebert R, Lopez de Munain A, Perez-Tur J, Nobile C (2003) Autosomal dominant lateral temporal epilepsy: clinical spectrum, new epitempin mutations, and genetic heterogeneity in seven European families. Epilepsia 44:1289–1297

10.

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

11.

Kajava AV (1998) Structural diversity of leucine-rich repeat proteins. J Mol Biol 277:519–527CrossRefPubMed

12.

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

13.

Skradski SL, Clark AM, Jiang H, White HS, Fu YH, Ptacek LJ (2001) A novel gene causing a mendelian audiogenic mouse epilepsy. Neuron 31:537–544

14.

Staub E, Perez-Tur J, Siebert R, Nobile C, Moschonas NK, Deloukas P, Hinzmann B (2002) The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders. Trends Biochem Sci 27:441–444

15.

Scheel H, Tomiuk S, Hofmann K. A common protein interaction domain links two recently identified epilepsy genes. Hum Mol Genet 11:1757–1762

16.

Hedera P, Abou-Khalil B, Crunk AE, Taylor KA, Haines JL, Sutcliffe JS (2004) Autosomal dominant lateral temporal epilepsy: two families with novel mutations in the LGI1 gene. Epilepsia 45:218–222

17.

Winawer MR, Ottman R, Hauser WA, Pedley TA (2000) Autosomal dominant partial epilepsy with auditory features: defining the phenotype. Neurology 54:2173–2176

18.

Gu W, Wevers A, Schroder H, Grzeschik KH, Derst C, Brodtkorb E, de Vos R, Steinlein OK (2002) The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins. FEBS Lett 519:71–76

19.

Winawer MR, Martinelli Boneschi F, Barker-Cummings C, Lee JH, Liu J, Mekios C, Gilliam TC, Pedley TA, Hauser WA, Ottman R (2002) Four new families with autosomal dominant partial epilepsy with auditory features: clinical description and linkage to chromosome 10q24. Epilepsia 43:60–67

20.

Poza JJ, Saenz A, Martinez-Gil A, Cheron N, Cobo AM, Urtasun M, Marti-Masso JF, Grid D, Beckmann JS, Prud’homme JF, Lopez de Munain A (1999) Autosomal dominant lateral temporal epilepsy: clinical and genetic study of a large Basque pedigree linked to chromosome 10q. Ann Neurol 45:182–188

21.

Michelucci R, Passarelli D, Pitzalis S, Dal Corso G, Tassinari CA, Nobile C (2000) Autosomal dominant partial epilepsy with auditory features: description of a new family. Epilepsia 41:967–970

22.

Berkovic SF, Izzillo P, McMahon JM, Harkin LA, McIntosh AM, Phillips HA, Briellmann RS, Wallace RH, Mazarib A, Neufeld MY, Korczyn AD, Scheffer IE, Mulley JC (2004) LGI1 mutations in temporal lobe epilepsies. Neurology 62:1115–1119

23.

Fertig E, Lincoln A, Martinuzzi A, Mattson RH, Hisama FM (2003) Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features. Neurology 60:1687–1690PubMed

24.

Kobayashi E, Santos NF, Torres FR, Secolin R, Sardinha LA, Lopez-Cendes I, Cendes F (2003) Magnetic resonance imaging abnormalities in familial temporal lobe epilepsy with auditory auras. Arch Neurol 60:1546–1551

25.

Kobayashi E (2004) Erratum. Arch Neurol 61:199

26.

Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823PubMed

27.

Bigner SH, Vogelstein B (1990) Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma. Brain Pathol 1:12–18PubMed

28.

James CD, He J, Carlbom E, Mikkelsen T, Ridderheim PA, Cavenee WK, Collins VP (1990) Loss of genetic information in central nervous system tumors common to children and young adults. Genes Chromosomes Cancer 2:94–102

29.

Karlbom AE, James CD, Boethius J, Cavenee WK, Collins VP, Nordenskjold M, Larsson C (1993) Loss of heterozygosity in malignant gliomas involved at least three distinct regions on chromosome 10. Hum Genet 92:169–174

30.

Rasheed BK, Fuller GN, Friedman AH, Bigner DD, Bigner SH (1992) Loss of heterozygosity for 10q loci in human gliomas. Genes Chromosomes Cancer 5:75–82

31.

Zainuddin N, Jaafart H, Isa MN, Abdullah JM (2004) Loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in Malays with malignant glioma. Neurol Res 26:88–92

32.

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

33.

Besleaga R, Montesinos-Rongen M, Perez-Tur J, Siebert R, Deckert M (2003) Expression of the LGI1 gene product in astrocytic gliomas: downregulation with malignant progression. Virchows Arch 443:561–564

34.

Krex D, Hauses M, Appelt H, Mohr B, Ehninger G, Schackert HK, Schackert G (2002) Physical and functional characterization of the human LGI1 gene and its possible role in glioma development. Acta Neuropathol 103:255–266

35.

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

36.

Kunapuli P, Kasyapa CS, Hawthorn L, Cowell JK (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

37.

Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494

38.

Nakada M, Nakamura H, Ikeda E, Fujimoto N, Yamashita J, Sato H, Seiki M, Okada Y (1999) Expression and tissue localization of membrane-type 1, 2, and 3 matrix metalloproteinases in human astrocytic tumors. Am J Pathol 154:417–428

39.

Del Bigio MR, Tchelingerian JL, Jacque CM (1999) Expression of extracellular matrix degrading enzymes during migration of xenografted brain cells. Neuropathol Appl Neurobiol 25:54–62PubMed

40.

Steeg PS (2003) Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer 3:55–63

41.

Brodtkorb E, Nakken KO, Steinlein OK (2003) No evidence for a seriously increased malignancy risk in LGI1-caused epilepsy. Epilepsy Res 56:205–208CrossRefPubMed

42.

Sherr CJ (2004) Principles of tumor suppression. Cell 116:235–246

43.

McMillan DR, White PC (2004) Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice. Mol Cell Neurosci 26:322–329

44.

Nakayama J, Hamano K, Iwasaki N, Nakahara S, Horigome Y, Saitoh H, Aoki T, Maki T, Kikuchi M, Migita T, Ohto T, Yokouchi Y, Tanaka R, Hasegawa M, Matsui A, Hamaguchi H, Arinami T (2000) Significant evidence for linkage of febrile seizures to chromosome 5q14–q15. Hum Mol Genet 9:87–91

45.

Nakayama J, Fu YH, Clark AM, Nakahara S, Hamano K, Iwasaki N, Matsui A, Arinami T, Ptacek LJ (2002) A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann Neurol 52:654–657PubMed

46.

Weston MD, Luijendijk MW, Humphrey KD, Moller C, Kimberling WJ (2004) Mutations in the -1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am J Hum Genet 74:357–366CrossRefPubMed

47.

Zheng QY, Johnson KR, Erway LC (1999) Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear Res 130:94–107CrossRefPubMed

Title: LGI1: a gene involved in epileptogenesis and glioma progression?
Authors: W. Gu
E. Brodtkorb
T. Piepoli
G. Finocchiaro
O. K. Steinlein
Publication date: 01-05-2005
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 2/2005
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-005-0216-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

LGI1: a gene involved in epileptogenesis and glioma progression?

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2005

Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia

Diagnosis of Pelizaeus–Merzbacher disease: detection of proteolipid protein gene copy number by real-time PCR

A novel NIPA1 mutation associated with a pure form of autosomal dominant hereditary spastic paraplegia

Novel mutations and repeated findings of mutations in familial Alzheimer disease

The urokinase-plasminogen activator (PLAU) gene is not associated with late onset Alzheimer’s disease

Creutzfeldt-Jakob disease associated with an R148H mutation of the prion protein gene