Towards the identification of a genetic basis for Landau‐Kleffner syndrome. Issue 6 (14th May 2014)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Epilepsia. Volume 55:Issue 6(2014:Jun.)
• Page Start: 858
• Page End: 865
• Publication Date: 2014-05-14
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12645
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12645-abs-0001"> <title>Summary</title> <sec id="epi12645-sec-0001" sec-type="section"> <title>Objective</title> <p>To establish the genetic basis of Landau‐Kleffner syndrome (LKS) in a cohort of two discordant monozygotic (MZ) twin pairs and 11 isolated cases.</p> </sec> <sec id="epi12645-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="epi12645-sec-0003" sec-type="section"> <title>Results</title> <p>A variant (cG1553A) was found in a single patient in the <italic>GRIN2A</italic> 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 <italic>RELN</italic>, <italic> BSN, EPHB2, </italic> and <italic>NID2</italic>.</p> </sec> <sec id="epi12645-sec-0004" sec-type="section"> <title>Significance</title> <p>A single mutation was identified in the <italic>GRIN2A</italic> gene. This study has identified a number of additional candidate genes including <italic>RELN</italic>, <italic> BSN</italic>, <italic> EPHB2, </italic> and <italic>NID2</italic>.</p> <p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <ext-link ext-link-type="uri" xlink:href="http://onlinelibrary.wiley.com/doi/10.1111/epi.12645/suppinfo" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">here</ext-link>.</p> </sec> </abstract>