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    ABSTRACT: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare familial partial epilepsy syndrome with onset in the second or third decades of life characterized by recurrent auditory auras and/or other symptoms suggesting a lateral temporal onset. Mutations in the leucine-rich, glioma inactivated 1 gene (LGI1) on chromosome 10q have been identified in approximately 50% of families with ADPEAF. In the literature a total of 25 LGI1 mutations have been described. The mechanisms by which LGI1 mutations cause epilepsy remain unclear. Among the various diagnostic techniques it is important to obtain an electroencephalogram and long-latency auditory evoked potentials. The prognosis is good and the treatment is based on carbamazepine, phenytoin and valproate.
    Hearing, Balance and Communication. 05/2012; 10(2).
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    ABSTRACT: To clinically and genetically characterize a large Brazilian family with autosomal dominant partial epilepsy with auditory features (ADPEAF) not related to leucine-rich, glioma-inactivated 1 (LGI1) gene. Seventy family members (four married-ins) participating in the study were assessed by a detailed clinical interview and a complete neurologic examination. Genetic mapping was conducted through autosome-wide single nucleotide polymorphism (SNP) genotyping and subsequent linkage analysis on 16 and haplotype analysis on 25 subjects, respectively. The pedigree comprised 15 affected members, of whom 11 were included in the study (male/female: 6/5; mean age 39.5 years). All but two (III:22 and IV:92) had focal seizures with auditory aura followed by secondary generalization in 44.4%. The mean age at onset of epilepsy seizures was 13.7 years. Initial autosome-wide SNP linkage analysis conducted on 12 subjects (8 affected) pointed to a single genomic region on chromosome 19 with a maximum multipoint logarithm of the odds (LOD) score of 2.60. Further refinement of this region through SNP and microsatellite genotyping on 16 subjects (11 affected) increased the LOD score to 3.41, thereby establishing 19q13.11-q13.31 as a novel ADPEAF locus. Haplotype analysis indicated that the underlying mutation is most likely located in a 9.74 Mb interval between markers D19S416 and D19S420. Sequence analysis of the most prominent candidate genes within this critical interval (SCN1B, LGI4, KCNK6, and LRFN1) did not reveal any mutation. This study disclosed a novel ADPEAF locus on chromosome 19q13.11-q13.31, contributing to future identification of a second dominant gene for this epileptic syndrome. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
    Epilepsia 03/2014; · 3.96 Impact Factor
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    ABSTRACT: A new leucine-rich glioma-inactivated 1 gene (LGI1) mutation inducing an amino acid sequence substitution was found in a Korean family with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We report the clinical features and characteristics of this newly identified LGI1 mutation. Clinical data were collected from a large ADLTE family. All exons and flanking regions of the LGI1 gene were directly sequenced. 243 healthy controls were screened for the putative mutation. The 'Sorting Tolerant From Intolerant' algorithm was employed for the prediction of mutated LGI1 protein stability. LGI1 protein secretion was confirmed in vitro by immunoblotting assay. The main clinical characteristics included a young age at onset (mean, 12.4 years), diverse phenotypic manifestations, the occurrence of generalized tonic-clonic seizures, and a favorable prognosis. The genetic analysis detected a nonsynonymous single nucleotide polymorphism of c.137G>T coding for p.C46F in the five affected family members. This variant was not found in the normal control population and one unaffected family member. All the amino acids substituted for cysteine at position 46 of the LGI1 protein were predicted to damage protein stability in in silico analysis. Mutated C46F protein was retained within the cell at the immunoblotting assay. We identified a new LGI1 mutation in a large Korean ADLTE family which appeared to be involved in the development of epilepsy through suppressing LGI1 protein secretion.
    Seizure 10/2013; · 2.00 Impact Factor