Neurological disorder-associated genetic variants in individuals with psychogenic nonepileptic seizures.
Adult
Amino Acid Substitution
Chromosomes, Human
/ genetics
Epilepsies, Partial
/ genetics
Epilepsy, Generalized
/ genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
/ methods
Histone-Lysine N-Methyltransferase
/ genetics
Humans
Male
Middle Aged
Receptors, GABA-A
/ genetics
Seizures
/ genetics
Sequence Deletion
Exome Sequencing
/ methods
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 09 2020
16 09 2020
Historique:
received:
30
04
2020
accepted:
24
08
2020
entrez:
17
9
2020
pubmed:
18
9
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Psychogenic nonepileptic seizures (PNES) are diagnosed in approximately 30% of patients referred to tertiary care epilepsy centers. Little is known about the molecular pathology of PNES, much less about possible underlying genetic factors. We generated whole-exome sequencing and whole-genome genotyping data to identify rare, pathogenic (P) or likely pathogenic (LP) variants in 102 individuals with PNES and 448 individuals with focal (FE) or generalized (GE) epilepsy. Variants were classified for all individuals based on the ACMG-AMP 2015 guidelines. For research purposes only, we considered genes associated with neurological or psychiatric disorders as candidate genes for PNES. We observe in this first genetic investigation of PNES that six (5.88%) individuals with PNES without coexistent epilepsy carry P/LP variants (deletions at 10q11.22-q11.23, 10q23.1-q23.2, distal 16p11.2, and 17p13.3, and nonsynonymous variants in NSD1 and GABRA5). Notably, the burden of P/LP variants among the individuals with PNES was similar and not significantly different to the burden observed in the individuals with FE (3.05%) or GE (1.82%) (PNES vs. FE vs. GE (3 × 2 χ
Identifiants
pubmed: 32938993
doi: 10.1038/s41598-020-72101-8
pii: 10.1038/s41598-020-72101-8
pmc: PMC7495430
doi:
Substances chimiques
GABRA6 protein, human
0
Receptors, GABA-A
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
NSD1 protein, human
EC 2.1.1.43
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15205Subventions
Organisme : NCATS NIH HHS
ID : CTSA UL1TR000439
Pays : United States
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