Epilepsia · 2014
Towards the identification of a genetic basis for Landau-Kleffner syndrome.
СтатьяПоддержка исследования: вне правительства СШАTwin StudyНазвание и аннотация: Перевод в очереди
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Conroy Judith, McGettigan Paul A, McCreary Dara, Shah Naisha, Collins Kevin, Parry-Fielder Bronwyn, Moran Margaret, Hanrahan Donncha, Deonna Thierry W, Korff Christian M, Webb David, Ennis Sean, Lynch Sally A, King Mary D
Аннотация
OBJECTIVE: To establish the genetic basis of Landau-Kleffner syndrome (LKS) in a cohort of two discordant monozygotic (MZ) twin pairs and 11 isolated cases.
METHODS: We used a multifaceted approach to identify genetic risk factors for LKS. Array comparative genomic hybridization (CGH) was performed using the Agilent 180K array. Whole genome methylation profiling was undertaken in the two discordant twin pairs, three isolated LKS cases, and 12 control samples using the Illumina 27K array. Exome sequencing was undertaken in 13 patients with LKS including two sets of discordant MZ twins. Data were analyzed with respect to novel and rare variants, overlapping genes, variants in reported epilepsy genes, and pathway enrichment.
RESULTS: A variant (cG1553A) was found in a single patient in the GRIN2A gene, causing an arginine to histidine change at site 518, a predicted glutamate binding site. Following copy number variation (CNV), methylation, and exome sequencing analysis, no single candidate gene was identified to cause LKS in the remaining cohort. However, a number of interesting additional candidate variants were identified including variants in RELN, BSN, EPHB2, and NID2.
SIGNIFICANCE: A single mutation was identified in the GRIN2A gene. This study has identified a number of additional candidate genes including RELN, BSN, EPHB2, and NID2. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
METHODS: We used a multifaceted approach to identify genetic risk factors for LKS. Array comparative genomic hybridization (CGH) was performed using the Agilent 180K array. Whole genome methylation profiling was undertaken in the two discordant twin pairs, three isolated LKS cases, and 12 control samples using the Illumina 27K array. Exome sequencing was undertaken in 13 patients with LKS including two sets of discordant MZ twins. Data were analyzed with respect to novel and rare variants, overlapping genes, variants in reported epilepsy genes, and pathway enrichment.
RESULTS: A variant (cG1553A) was found in a single patient in the GRIN2A gene, causing an arginine to histidine change at site 518, a predicted glutamate binding site. Following copy number variation (CNV), methylation, and exome sequencing analysis, no single candidate gene was identified to cause LKS in the remaining cohort. However, a number of interesting additional candidate variants were identified including variants in RELN, BSN, EPHB2, and NID2.
SIGNIFICANCE: A single mutation was identified in the GRIN2A gene. This study has identified a number of additional candidate genes including RELN, BSN, EPHB2, and NID2. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Предметные рубрики MeSH
AdolescentAdultCalcium-Binding ProteinsCell Adhesion MoleculesCell Adhesion Molecules, NeuronalChildComparative Genomic HybridizationExtracellular Matrix ProteinsFemaleGenetic Predisposition to DiseaseHumansLandau-Kleffner SyndromeMaleNerve Tissue ProteinsOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideReceptor, EphB2Receptors, N-Methyl-D-AspartateReelin ProteinSerine EndopeptidasesTwins, MonozygoticYoung Adult