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.[5]
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[6][7] mutation analysis of affected members in these families[8][9][10] demonstrated LGI1 was a major cause of the disease.
More recently, LGI1 has been shown to be the major target of human autoantibodies[11][12][13] 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.
^Wilson MH, Puranam RS, Ottman R, Gilliam C, Limbird LE, George AL, McNamara JO (December 1998). "Evaluation of the alpha(2A)-adrenergic receptor gene in a heritable form of temporal lobe epilepsy". Neurology. 51 (6): 1730–1. doi:10.1212/wnl.51.6.1730. PMID9855534. S2CID85601127.
^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 (May 2011). "Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis". Annals of Neurology. 69 (5): 892–900. doi:10.1002/ana.22307. PMID21416487. S2CID13775077.
Gu W, Brodtkorb E, Steinlein OK (September 2002). "LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures". Annals of Neurology. 52 (3): 364–7. doi:10.1002/ana.10280. PMID12205652. S2CID2957451.
Pizzuti A, Flex E, Di Bonaventura C, Dottorini T, Egeo G, Manfredi M, Dallapiccola B, Giallonardo AT (March 2003). "Epilepsy with auditory features: a LGI1 gene mutation suggests a loss-of-function mechanism". Annals of Neurology. 53 (3): 396–9. doi:10.1002/ana.10492. PMID12601709. S2CID26216565.
Fertig E, Lincoln A, Martinuzzi A, Mattson RH, Hisama FM (May 2003). "Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features". Neurology. 60 (10): 1687–90. doi:10.1212/01.wnl.0000063324.39980.4a. PMID12771268. S2CID41281964.
Kunapuli P, Chitta KS, Cowell JK (June 2003). "Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene". Oncogene. 22 (26): 3985–91. doi:10.1038/sj.onc.1206584. PMID12821932. S2CID6720407.
Bisulli F, Tinuper P, Scudellaro E, Naldi I, Bagattin A, Avoni P, Michelucci R, Nobile C (September 2004). "A de novo LGI1 mutation in sporadic partial epilepsy with auditory features". Annals of Neurology. 56 (3): 455–6. doi:10.1002/ana.20218. PMID15349881. S2CID26953058.
