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Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis.
- Source :
-
Epilepsia [Epilepsia] 2015 Mar; Vol. 56 (3), pp. e26-32. Date of Electronic Publication: 2015 Feb 17. - Publication Year :
- 2015
-
Abstract
- Fever-associated syndromic epilepsies ranging from febrile seizures plus (FS+) to Dravet syndrome have a significant genetic component. However, apart from SCN1A mutations in >80% of patients with Dravet syndrome, the genetic underpinnings of these epilepsies remain largely unknown. Therefore, we performed a genome-wide screening for copy number variations (CNVs) in 36 patients with SCN1A-negative fever-associated syndromic epilepsies. Phenotypes included Dravet syndrome (n = 23; 64%), genetic epilepsy with febrile seizures plus (GEFS+) and febrile seizures plus (FS+) (n = 11; 31%) and unclassified fever-associated epilepsies (n = 2; 6%). Array comparative genomic hybridization (CGH) was performed using Agilent 4 × 180K arrays. We identified 13 rare CNVs in 8 (22%) of 36 individuals. These included known pathogenic CNVs in 4 (11%) of 36 patients: a 1q21.1 duplication in a proband with Dravet syndrome, a 14q23.3 deletion in a proband with FS+, and two deletions at 16p11.2 and 1q44 in two individuals with fever-associated epilepsy with concomitant autism and/or intellectual disability. In addition, a 3q13.11 duplication in a patient with FS+ and two de novo duplications at 7p14.2 and 18q12.2 in a patient with atypical Dravet syndrome were classified as likely pathogenic. Six CNVs were of unknown significance. The identified genomic aberrations overlap with known neurodevelopmental disorders, suggesting that fever-associated epilepsy syndromes may be a recurrent clinical presentation of known microdeletion syndromes.<br /> (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)
- Subjects :
- Adolescent
Adult
Child
Child, Preschool
Chromosome Aberrations
Chromosome Deletion
Comparative Genomic Hybridization
Female
Genetic Association Studies
Humans
Male
Middle Aged
Phenotype
Young Adult
DNA Copy Number Variations genetics
Epilepsy etiology
Epilepsy genetics
Fever complications
NAV1.1 Voltage-Gated Sodium Channel genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-1167
- Volume :
- 56
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Epilepsia
- Publication Type :
- Academic Journal
- Accession number :
- 25690317
- Full Text :
- https://doi.org/10.1111/epi.12920