Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy

Ayerdi-Izquierdo, Ana; Stavrides, George; Sellés-Martínez, J.J.; Larrea, Luís; Bovo, Giorgia; Munáin, Adolfo López de; Bisulli, Francesca; Martí-Massó, J.F.; Michelucci, Roberto; Poza, Juan José; Tinuper, Paolo; Stephani, Ulrich; Striano, Pasquale; Striano, Salvatore; Staub, Eike; Sarafidou, Theologia; Hinzmann, Bernd; Moschonas, Nicholas Κ.; Siebert, Reiner; Deloukas, Panos; Nobile, Carlo; Pérez-Tur, Jordi

doi:10.1016/j.eplepsyres.2006.03.008

Cited by 6 publications

(4 citation statements)

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“…The role of defective LGI1 in the origin of the epileptic focus from the lateral temporal lobe remains unclear, and efforts to identify the genetic defect in LGI1 ‐negative ADPEAF patients have hitherto been inconclusive. In fact, genetic studies failed to disclose mutations in any of the several candidate genes evolutionarily or functionally related to LGI1 , whereas the small size of most LGI1 ‐negative ADPEAF families has generally hampered gene mapping through linkage analysis. Finally, identification of additional genes underlying this disorder might be made particularly challenging by the fact that a fraction of the LGI1 ‐negative families may have a complex genetic architecture, thus implicating the oligogenic inheritance of multiple low‐penetrance mutations.…”

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Autosomal dominant partial epilepsy with auditory features: A new locus on chromosome 19q13.11–q13.31

et al. 2014

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SUMMARYObjective: 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. Methods: 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. Results: 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. Significance: 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.

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Autosomal dominant partial epilepsy with auditory features: A new locus on chromosome 19q13.11–q13.31

et al. 2014

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“…By immunohistochemical analysis, we demonstrated that the LGI1 protein, which contains several leucine‐rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we have provided evidence for genetic heterogeneity within this disorder, several other families with a phenotype consistent with this type of epilepsy lacking mutations in the LGI1 gene (Michelucci et al., ; Ayerdi‐Izquierdo et al., ).…”

Section: Neurogenetic Disorders In the Basque Countrymentioning

confidence: 99%

Neurogenetic Disorders in the Basque Population

Massó

Zarranz

Otaegui

et al. 2014

Annals of Human Genetics

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SummaryIn the molecular era, the study of neurogenetic disorders in relict populations provides an opportunity to discover new genes by linkage studies and to establish clearer genotype-phenotype correlations in large cohorts of individuals carrying the same mutation. The Basque people are one of the most ancient populations living in Europe and represent an excellent resource for this type of analysis in certain genetic conditions. Our objective was to describe neurogenetic disorders reported in the Basque population due to the presence of ancestral mutations or an accumulation of cases or both. We conducted a search in PubMed with the terms: Basque, neurogenetic disorders, genetic risk, and neurological disorders. We identified nine autosomal and two recessive disorders in the Basque population attributable to ancestral mutations (such as in PNRP, PARK8, FTDP-TDP43, LGMD2A, VCP, c9ORF72, and CMT4A), highly prevalent (DM1) or involving unique mutations (PARK1 or MAPT). Other genes were reported for their role as protective/risk factors in complex diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. At the present time, when powerful sequencing techniques are identifying large numbers of genetic variants associated with unique phenotypes, the scrutiny of these findings in genetically homogeneous populations can help analyze genotype-phenotype correlations.

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“…However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin gene or have evidence for linkage to the 10q24 locus. (13) Previous studies have shown evidence of association of LGI-4 polymorphism with Benign Familial Infantile Convulsions (BFIC) (9) and childhood absence epilepsy. (14) In this study, we tested whether genetic variations in the GABRG2 and LGI-4 gene confers susceptibility to idiopathic epilepsy and febrile seizures or not in Indian population.…”

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confidence: 99%

Association Analysis of 2 Subunit of -Aminobutyric Acid Type- A Receptor (Gabrg2) and Leucine-Rich Glioma-Inactivated 4 Gene (Lgi-4) Polymorphisms With Idiopathic Epilepsies and Febrile Seizures

Gupta¹,

Kumar²,

Chandra³

2018

jemds

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BACKGROUND Epilepsy is the most common neurological disorder affecting 60 million people worldwide and in an estimated 40% of whom it is genetically determined. Idiopathic epilepsies are those in which genetic aetiology is likely or proven. An alteration of GABA-ergic neurotransmission has been implicated as an aetiologic factor in epileptogenesis, while LGI-4 (Leucine Rich Glioma Inactivated 4) is not homologous to any known ion channel and the mechanism by which it causes epilepsy is unknown. LGI-4 belongs to a super family LRR (Leucine Rich Repeats) proteins and suspected to have a role in peripheral nerve myelination. The authors aimed to determine whether genetic variations in the GABRG2 and LGI-4 gene confers susceptibility to idiopathic epilepsy and febrile seizures or not. MATERIALS AND METHODS In this case control study, samples of 30 cases and 42 controls were taken. Allelic frequencies were expressed as a percentage of the total number of alleles. Genotypes and allelic frequencies for c.588C/T in fifth exon of gene GABRG2 (SNP211037, Asn196Asn) and c.1914GC/AT located in ninth exon of the gene LGI-4 were compared in both groups. RESULTS Association analysis of GABRG-2 polymorphism between CC, CT and TT genotypes statistically showed insignificant result as χ 2 value was 0.12 and p value was > 0.05. Association analysis of LGI-4 polymorphism between GC/GC, GC/AT and AT/AT genotypes statistically showed insignificant result as χ 2 value was 0.51 and p value was > 0.05. CONCLUSION It was concluded that GABRG2 and LGI-4 polymorphisms were not the susceptibility factors for idiopathic epilepsies and febrile seizures. KEY WORDS γ-Aminobutyric Acid Type A Receptor (GABRG2) Polymorphism, Leucine-Rich Glioma-Inactivated 4 Gene (LGI-4) Polymorphism, Idiopathic Epilepsies and Febrile Seizures. HOW TO CITE THIS ARTICLE: Gupta G, Kumar N, Chandra R. Association analysis of γ2 subunit of γ-aminobutyric acid type-a receptor (GABRG2) and leucine-rich glioma-inactivated 4 gene (LGI-4) polymorphisms with idiopathic epilepsies and febrile seizures.

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Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy

Cited by 6 publications

References 26 publications

Autosomal dominant partial epilepsy with auditory features: A new locus on chromosome 19q13.11–q13.31

Autosomal dominant partial epilepsy with auditory features: A new locus on chromosome 19q13.11–q13.31

Neurogenetic Disorders in the Basque Population

Association Analysis of 2 Subunit of -Aminobutyric Acid Type- A Receptor (Gabrg2) and Leucine-Rich Glioma-Inactivated 4 Gene (Lgi-4) Polymorphisms With Idiopathic Epilepsies and Febrile Seizures

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