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    • "Heterozygous variations in leucine-rich, glioma-inactivated 1 (LGI1) gene have been implicated both in ADTLE and IPEAF (Dazzo et al., 2015a). Substantial proportion of ADLTE families (up to 50%) and only very rare IPEAF cases carry inherited or de novo point mutations in LGI1, respectively (Michelucci et al., 2003;Bisulli et al., 2004b;Dazzo et al., 2015a). Small LGI1 micro-rearrangements have also been spotted in ADTLE (Fanciulli et al., 2012;Dazzo et al., 2015a). "
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    ABSTRACT: Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is an autosomal dominant epileptic syndrome characterized by focal seizures with auditory or aphasic symptoms. The same phenotype is also observed in a sporadic form of lateral temporal lobe epilepsy (LTLE), namely idiopathic partial epilepsy with auditory features (IPEAF). Heterozygous mutations in LGI1 account for up to 50% of ADLTE families and only rarely observed in IPEAF cases. In this study, we analysed a cohort of 26 individuals with LTLE diagnosed according to the following criteria: focal epilepsy with auditory aura and absence of cerebral lesions on brain MRI. All patients underwent clinical, neuroradiological and electroencephalography examinations and afterwards they were screened for mutations in LGI1 gene. The single LGI1 mutation identified in this study is a novel missense variant (NM_005097.2: c.1013T>C; p.Phe338Ser) observed de novo in a sporadic patient. This is the first study involving clinical analysis of a LTLE cohort from Turkey and genetic contribution of LGI1 to ADLTE phenotype. Identification of rare LGI1 gene mutations in sporadic cases supports diagnosis as ADTLE and draws attention to potential familial clustering of ADTLE in suggestive generations, which is especially important for genetic counselling.
    Full-text · Article · Jan 2016 · Epilepsy research
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    • "More than 30 mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene have been associated with ADLTE, representing the genetic hallmark of this syndrome (Nobile et al., 2009). LGI1 mutations have also been found in 2 of >200 sporadic cases (Bisulli et al., 2004b; Michelucci et al., 2007). "
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    ABSTRACT: Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, headaches, intracerebral hemorrhages, and focal neurological deficits; they can also be clinically silent and occur as a sporadic or an autosomal dominant condition. Three genes have been identified as causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes 7q, 7p, and 3q. Here, we report an Italian family affected by CCM due to a MGC4607 gene mutation, on exon 4. All the affected subjects suffered from seizures, and some of them underwent surgery for removal of a cavernous angioma. Brain MRI showed multiple lesions consistent with CCMs in all patients. Spinal and cutaneous cavernous angiomas were present too. This report underlines the need for a careful interdisciplinarity among neurologists, neuroradiologists, neurosurgeons, geneticists, ophthalmologists, and dermatologists for a total evaluation of the different manifestations of familial CCM. This points out that only referral centers are organized to offer a multidisciplinary management of this disease.
    Full-text · Article · Apr 2015 · Journal of Molecular Neuroscience
    • "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.
    No preview · Article · Feb 2015 · Epilepsy Research
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