LGI1

The leucine-rich glioma inactivated -1 gene is rearranged as a result of translocations in glioblastoma cell lines. The protein contains a hydrophobic segment representing a putative transmembrane domain with the amino terminus located outside the cell. It also contains leucine-rich repeats with conserved cysteine-rich flanking sequences. This gene is predominantly expressed in neural tissues and its expression is reduced in low grade brain tumors and significantly reduced or absent in malignant gliomas.{{cite web | title = Entrez Gene: LGI1 leucine-rich, glioma inactivated 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9211| accessdate = }}

Since its earliest discovery, the LGI1 gene has been implicated in the control of cancer metastasis and in a predisposition to epilepsy. Following genetic linkage studies placing the hereditary form of autosomal dominant partial epilepsy with auditory features (ADPEAF) on chromosome region 10q24{{cite journal | vauthors = Ottman R, Risch N, Hauser WA, Pedley TA, Lee JH, Barker-Cummings C, Lustenberger A, Nagle KJ, Lee KS, Scheuer ML | title = Localization of a gene for partial epilepsy to chromosome 10q | journal = Nature Genetics | volume = 10 | issue = 1 | pages = 56–60 | date = May 1995 | pmid = 7647791 | pmc = 2823475 | doi = 10.1038/ng0595-56 }}{{cite journal | vauthors = Wilson MH, Puranam RS, Ottman R, Gilliam C, Limbird LE, George AL, McNamara JO | title = Evaluation of the alpha(2A)-adrenergic receptor gene in a heritable form of temporal lobe epilepsy | journal = Neurology | volume = 51 | issue = 6 | pages = 1730–1 | date = December 1998 | pmid = 9855534 | doi = 10.1212/wnl.51.6.1730 | s2cid = 85601127 }} mutation analysis of affected members in these families{{cite journal | vauthors = 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 | title = Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features | journal = Nature Genetics | volume = 30 | issue = 3 | pages = 335–41 | date = March 2002 | pmid = 11810107 | pmc = 2606053 | doi = 10.1038/ng832 }}{{cite journal | vauthors = Ottman R, Winawer MR, Kalachikov S, Barker-Cummings C, Gilliam TC, Pedley TA, Hauser WA | title = LGI1 mutations in autosomal dominant partial epilepsy with auditory features | journal = Neurology | volume = 62 | issue = 7 | pages = 1120–6 | date = April 2004 | pmid = 15079011 | pmc = 1361770 | doi = 10.1212/01.wnl.0000120098.39231.6e }}{{cite journal | vauthors = Nobile C, Michelucci R, Andreazza S, Pasini E, Tosatto SC, Striano P | title = LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy | journal = Human Mutation | volume = 30 | issue = 4 | pages = 530–6 | date = April 2009 | pmid = 19191227 | doi = 10.1002/humu.20925 | s2cid = 25089540 | doi-access = free }} demonstrated LGI1 was a major cause of the disease.

More recently, LGI1 has been shown to be the major target of human autoantibodies{{cite journal | vauthors = Irani SR, Stagg CJ, Schott JM, Rosenthal CR, Schneider SA, Pettingill P, Pettingill R, Waters P, Thomas A, Voets NL, Cardoso MJ, Cash DM, Manning EN, Lang B, Smith SJ, Vincent A, Johnson MR | title = Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype | journal = Brain | volume = 136 | issue = Pt 10 | pages = 3151–62 | date = October 2013 | pmid = 24014519 | doi = 10.1093/brain/awt212 | doi-access = free }}{{cite journal | vauthors = Irani SR, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, Schott JM, Armstrong RJ, S Zagami A, Bleasel A, Somerville ER, Smith SM, Vincent A | title = Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis | journal = Annals of Neurology | volume = 69 | issue = 5 | pages = 892–900 | date = May 2011 | pmid = 21416487 | doi = 10.1002/ana.22307 | s2cid = 13775077 }}{{cite journal | vauthors = Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, Peles E, Buckley C, Lang B, Vincent A | title = 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 | journal = Brain | volume = 133 | issue = 9 | pages = 2734–48 | date = September 2010 | pmid = 20663977 | pmc = 2929337 | doi = 10.1093/brain/awq213 }} which immunoprecipitate voltage-gated potassium channel complexes from mammalian brain tissue. LGI1 antibodies are found in patients with limbic encephalitis and in patients with faciobrachial dystonic seizures (FBDS). FBDS are a recently described form of epilepsy which is characterized by frequent, brief seizures which affect the arm and face. They appear to be preferentially responsive to immunotherapy over anti-epileptic drugs.

LGI1 has been shown to interact with ADAM22, and DLG4.{{cite journal | vauthors = Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M | title = Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission | journal = Science | volume = 313 | issue = 5794 | pages = 1792–5 | date = September 2006 | pmid = 16990550 | doi = 10.1126/science.1129947 | bibcode = 2006Sci...313.1792F | s2cid = 33024022 }}

{{Clear}}

{{reflist|35em}}

{{refbegin|35em}}

• {{cite journal | vauthors = Staub E, Pérez-Tur J, Siebert R, Nobile C, Moschonas NK, Deloukas P, Hinzmann B | title = The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders | journal = Trends in Biochemical Sciences | volume = 27 | issue = 9 | pages = 441–4 | date = September 2002 | pmid = 12217514 | doi = 10.1016/S0968-0004(02)02163-1 }}
• {{cite journal | vauthors = Gu W, Brodtkorb E, Piepoli T, Finocchiaro G, Steinlein OK | title = LGI1: a gene involved in epileptogenesis and glioma progression? | journal = Neurogenetics | volume = 6 | issue = 2 | pages = 59–66 | date = May 2005 | pmid = 15827762 | doi = 10.1007/s10048-005-0216-5 | s2cid = 10999158 }}
• {{cite journal | vauthors = Chernova OB, Somerville RP, Cowell JK | title = A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors | journal = Oncogene | volume = 17 | issue = 22 | pages = 2873–81 | date = December 1998 | pmid = 9879993 | doi = 10.1038/sj.onc.1202481 | doi-access = free }}
• {{cite journal | vauthors = Morante-Redolat JM, Gorostidi-Pagola A, Piquer-Sirerol S, Sáenz A, Poza JJ, Galán 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, Martí-Massó JF, Kluwe L, Deloukas P, Moschonas NK, Michelucci R, Siebert R, Nobile C, Pérez-Tur J, López de Munain A | title = Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy | journal = Human Molecular Genetics | volume = 11 | issue = 9 | pages = 1119–28 | date = May 2002 | pmid = 11978770 | doi = 10.1093/hmg/11.9.1119 | doi-access = free }}
• {{cite journal | vauthors = Scheel H, Tomiuk S, Hofmann K | title = A common protein interaction domain links two recently identified epilepsy genes | journal = Human Molecular Genetics | volume = 11 | issue = 15 | pages = 1757–62 | date = July 2002 | pmid = 12095917 | doi = 10.1093/hmg/11.15.1757 | doi-access = free }}
• {{cite journal | vauthors = Gu W, Brodtkorb E, Steinlein OK | title = LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures | journal = Annals of Neurology | volume = 52 | issue = 3 | pages = 364–7 | date = September 2002 | pmid = 12205652 | doi = 10.1002/ana.10280 | s2cid = 2957451 }}
• {{cite journal | vauthors = Pizzuti A, Flex E, Di Bonaventura C, Dottorini T, Egeo G, Manfredi M, Dallapiccola B, Giallonardo AT | title = Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism | journal = Annals of Neurology | volume = 53 | issue = 3 | pages = 396–9 | date = March 2003 | pmid = 12601709 | doi = 10.1002/ana.10492 | s2cid = 26216565 }}
• {{cite journal | vauthors = Fertig E, Lincoln A, Martinuzzi A, Mattson RH, Hisama FM | title = Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features | journal = Neurology | volume = 60 | issue = 10 | pages = 1687–90 | date = May 2003 | pmid = 12771268 | doi = 10.1212/01.wnl.0000063324.39980.4a | s2cid = 41281964 }}
• {{cite journal | vauthors = Kunapuli P, Chitta KS, Cowell JK | title = Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene | journal = Oncogene | volume = 22 | issue = 26 | pages = 3985–91 | date = June 2003 | pmid = 12821932 | doi = 10.1038/sj.onc.1206584 | s2cid = 6720407 | doi-access = }}
• {{cite journal | vauthors = Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A | title = The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment | journal = Genome Research | volume = 13 | issue = 10 | pages = 2265–70 | date = October 2003 | pmid = 12975309 | pmc = 403697 | doi = 10.1101/gr.1293003 }}
• {{cite journal | vauthors = Hedera P, Abou-Khalil B, Crunk AE, Taylor KA, Haines JL, Sutcliffe JS | title = Autosomal dominant lateral temporal epilepsy: two families with novel mutations in the LGI1 gene | journal = Epilepsia | volume = 45 | issue = 3 | pages = 218–22 | date = March 2004 | pmid = 15009222 | doi = 10.1111/j.0013-9580.2004.47203.x | s2cid = 25416944 | doi-access = free }}
• {{cite journal | vauthors = Kunapuli P, Kasyapa CS, Hawthorn L, Cowell JK | title = LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway | journal = The Journal of Biological Chemistry | volume = 279 | issue = 22 | pages = 23151–7 | date = May 2004 | pmid = 15047712 | doi = 10.1074/jbc.M314192200 | doi-access = free }}
• {{cite journal | vauthors = 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 | title = LGI1 mutations in temporal lobe epilepsies | journal = Neurology | volume = 62 | issue = 7 | pages = 1115–9 | date = April 2004 | pmid = 15079010 | doi = 10.1212/01.wnl.0000118213.94650.81 | s2cid = 23725061 }}
• {{cite journal | vauthors = Bisulli F, Tinuper P, Scudellaro E, Naldi I, Bagattin A, Avoni P, Michelucci R, Nobile C | title = A de novo LGI1 mutation in sporadic partial epilepsy with auditory features | journal = Annals of Neurology | volume = 56 | issue = 3 | pages = 455–6 | date = September 2004 | pmid = 15349881 | doi = 10.1002/ana.20218 | s2cid = 26953058 }}

{{refend}}

• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=peaf GeneReviews/NCBI/NIH/UW entry on Autosomal Dominant Partial Epilepsy with Auditory Features]