Dataset Information

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

ABSTRACT: BACKGROUND:Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in GRIN2A accounting for >5% of cases. OBJECTIVE:To identify rare, causal CNV in patients with RE. METHODS:We used high-density SNP arrays to analyse the presence of rare CNVs in 186 patients with RE from the UK, the USA, Sardinia, Argentina and Kerala, India. RESULTS:We identified 84 patients with one or more rare CNVs, and, within this group, 14 (7.5%) with recurrent risk factor CNVs and 15 (8.0%) with likely pathogenic CNVs. Nine patients carried recurrent hotspot CNVs including at 16p13.11 and 1p36, with the most striking finding that four individuals (three from Sardinia) carried a duplication, and one a deletion, at Xp22.31. Five patients with RE carried a rare CNV that disrupted genes associated with other epilepsies (KCTD7, ARHGEF15, CACNA2D1, GRIN2A and ARHGEF4), and 17 cases carried CNVs that disrupted genes associated with other neurological conditions or that are involved in neuronal signalling/development. Network analysis of disrupted genes with high brain expression identified significant enrichment in pathways of the cholinergic synapse, guanine-exchange factor activation and the mammalian target of rapamycin. CONCLUSION:Our results provide a CNV profile of an ethnically diverse cohort of patients with RE, uncovering new areas of research focus, and emphasise the importance of studying non-western European populations in oligogenic disorders to uncover a full picture of risk variation.

SUBMITTER: Addis L

PROVIDER: S-EPMC6119347 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

Addis Laura L Sproviero William W Thomas Sanjeev V SV Caraballo Roberto H RH Newhouse Stephen J SJ Gomez Kumudini K Hughes Elaine E Kinali Maria M McCormick David D Hannan Siobhan S Cossu Silvia S Taylor Jacqueline J Akman Cigdem I CI Wolf Steven M SM Mandelbaum David E DE Gupta Rajesh R van der Spek Rick A RA Pruna Dario D Pal Deb K DK

Journal of medical genetics 20180522 9

<h4>Background</h4>Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in <i>GRIN2A</i> accounting for >5% of cases.<h4>Objective</h4>To identify rare, causal CNV in patients with RE.<h4>Methods</h4>We used high-density SNP arrays to analyse the presence of rare CNVs in 186 pati ...[more]

PMID: 29789371

Similar Datasets

Project description:Objective: To study the single nucleotide polymorphism rs662702 of ELP4-PAX6 in patients with idiopathic rolandic epilepsy syndromes (IRES) in China and explore the relationship between the distribution of rolandic spike sources and the single nucleotide polymorphism rs662702 in ELP4-PAX6. Methods: First, clinical information was obtained from patients diagnosed with IRES. Next, the single nucleotide polymorphism rs662702 of ELP4 was analyzed by using the Sanger method. Resting-state magnetoencephalography data were collected from 17 patients. We analyzed the epileptic spike sources using the single equivalent current dipole (SECD) model and determined the spike distributions across the whole brain. Finally, Fisher's test was performed to assess the correlation between the single nucleotide polymorphism rs662702 of ELP4-PAX6 and rolandic spike sources. Results: ELP4 rs662702 T alleles were found in 10.7% of IRES patients and occurred four times more frequently in these patients than in the healthy controls. TT homozygosity was found in one IRES patient (1.3%), while no TT homozygosity was found in the healthy control group. The IRES rolandic spike sources were unilateral in sixteen patients (94.1%) and were mainly located in the anterior central gyrus (58.8%). The spike source of patients without the ELP4 rs662702 T allele was correlated with the central region (p < 0.05). The rolandic spikes sources were significant correlated with the non-central gyrus (frontal and temporal lobes) in patients with the ELP4 rs662702 T allele (p < 0.05). Conclusion: The rolandic spike sources of the IRES patients with the ELP4 rs662702 T allele were significantly associated with the non-central gyrus, including the frontal and temporal lobes. Our study confirmed for the first time in vivo that ELP4 rs662702 T allele overexpression is correlated with the rolandic spike distribution in patients with IRES and provides important insights into how genetic abnormalities can lead to brain dysfunction and into the precise targeting of abnormal discharge sources in the brain.

Dataset Information

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

Publications

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets