A de novo LGI1 mutation causing idiopathic partial epilepsy with telephone-induced seizures

University of Naples Federico II, Napoli, Campania, Italy
Neurology (Impact Factor: 8.29). 07/2007; 68(24):2150-1. DOI: 10.1212/01.wnl.0000264932.44153.3c
Source: PubMed
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    • "Isolated patients with at least two lifetime seizures preceded by auditory auras, absence of structural brain abnormalities, and negative family history were classified as sporadic LTE cases (Bisulli et al., 2004b). Two sporadic LTE patients carrying LGI1 point mutations (Bisulli et al., 2004a; Michelucci et al., 2007) were excluded from analysis. "
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    ABSTRACT: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by prominent auditory or aphasic symptoms. Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE patients. Twenty-four ADLTE families and 140 sporadic LTE patients with no evidence of point mutations in LGI1 were screened for copy number alterations using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained familial and sporadic LTE patients were clinically investigated, and interictal EEG and MRI findings were obtained; probands were tested for LGI1 mutations by direct exon sequencing or denaturing high performance liquid chromatography. We identified a novel microdeletion spanning LGI1 exon 2 in a family with two affected members, both presenting focal seizures with visual symptoms. Also, we identified a novel LGI1 missense mutation (c.1118T>C; p.L373S) in a newly ascertained family with focal seizures with prominent visual auras, and another missense mutation (c.856T>C; p.C286R) in a sporadic patient with auditory seizures. We describe two novel ADLTE families with predominant visual auras segregating pathogenic LGI1 mutations. These findings support the notion that, in addition to auditory symptoms, other types of auras can be found in patients carrying LGI1 mutations. The identification of a novel microdeletion in LGI1, the second so far identified, suggests that LGI1 microrearrangements may not be exceptional. Copyright © 2014 Elsevier B.V. All rights reserved.
    Epilepsy Research 02/2015; 110C:132-138. DOI:10.1016/j.eplepsyres.2014.12.004 · 2.02 Impact Factor
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    • "In some patients, seizures are induced by acoustic stimuli such as sudden noises or answering the phone (Winawer et al., 2000; Michelucci et al., 2003, 2007), indicating a lateral temporal lobe onset. Some MRI studies have reported developmental abnormalities in the left Abbreviations: ADLTE, autosomal dominant lateral temporal lobe epilepsy; AGS, audiogenic seizures; EEG, electroencephalography; ENU, N-ethyl-N-nitrosourea; GTCS, generalized tonic–clonic seizures; IR, immunoreactivity; Lgi1, leucine-rich, glioma inactivated 1. * Corresponding author at: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. "
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    ABSTRACT: Mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene have been identified in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We previously reported that Lgi1 mutant rats, carrying a missense mutation (L385R) generated by gene-driven N-ethyl-N-nitrosourea (ENU) mutagenesis, showed generalized tonic-clonic seizures (GTCS) in response to acoustic stimuli. In the present study, we assessed clinically-relevant features of Lgi1 heterozygous mutant rats (Lgi1(L385R/+)) as an animal model of ADLTE. First, to explore the focus of the audiogenic seizures, we performed electroencephalography (EEG) and brain Fos immunohistochemistry in Lgi1(L385R/+) and wild type rats. EEG showed unique seizure patterns (e.g., bilateral rhythmic spikes) in Lgi1(L385R/+) rats with GTCS. An elevated level of Fos expression indicated greater neural excitability to acoustic stimuli in Lgi1(L385R/+) rats, especially in the temporal lobe, thalamus and subthalamic nucleus. Finally, microarray analysis revealed a number of differentially expressed genes that may be involved in epilepsy. These results suggest that Lgi1(L385R/+) rats are useful as an animal model of human ADLTE.
    Neuroscience Research 01/2014; 80(1). DOI:10.1016/j.neures.2013.12.008 · 1.94 Impact Factor
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    • "Interestingly, 50% of ADLTE families did not show any LGI1 mutations [12]. Moreover, de novo LGI1 mutations in unrelated sporadic TLE cases with auditory features, also called idiopathic partial epilepsy with auditory features (IPEAF) [13], account for about 2% of cases only [14]. A recent study, evaluating LGI1 promoter, prodynorphin (PDYN), and GABA (B) receptor 1 (GABBR1) genes in 104 sporadic IPEAF, did not show any statistically significant differences between patients and controls [15] "
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    ABSTRACT: Temporal lobe epilepsy (TLE) is usually regarded as a polygenic and complex disorder. To understand its genetic component, numerous linkage analyses of familial forms and association studies of cases versus controls have been conducted since the middle of the nineties. The present paper lists genetic findings for TLE from the initial segregation analysis to the most recent results published in May 2011. To date, no genes have been clearly related to TLE despite many efforts to do so. However, it is vital to continue replication studies and collaborative attempts to find significant results and thus determine which gene variant combination plays a definitive role in the aetiology of TLE.
    02/2012; 2012(2090-1348):863702. DOI:10.1155/2012/863702
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