Neurological disorder-associated genetic variants in individuals with psychogenic nonepileptic seizures
Abstract number :
817
Submission category :
12. Genetics / 12A. Human Studies
Year :
2020
Submission ID :
2423152
Source :
www.aesnet.org
Presentation date :
12/7/2020 9:07:12 AM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Costin Leu, Cleveland Clinic; Jocelyn F. Bautista - Neurological Institute, Cleveland Clinic; Monica Sudarsanam - Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic; Lisa-Marie Niestroj - Cologne Center for Genomics (CCG), University
Rationale:
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.
Method:
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.
Results:
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, 17p13.3 disrupting the PAFAH1B1 gene, and nonsynonymous variants in NSD1 and GABRA5). Notably, we did not observe significant differences in the burden of P/LP variants that affect genes associated with epilepsy, neurological disorders, or psychiatric disorders among the study groups (PNES: 5.88%; FE: 3.05%; GE: 1.82%; PNES vs. FE vs. GE (3x2 χ2), P=0.30; PNES vs. epilepsy (2x2 χ2), P=0.14).
Conclusion:
The presence of variants in genes associated with monogenic forms of neurological and psychiatric disorders in individuals with PNES shows that genetic factors are likely to play a role in PNES or its comorbidities. Future large-scale genetic research studies are needed to further corroborate these interesting findings in PNES.
Funding:
:This work was supported by institutional funding from the Cleveland Clinic Foundation. RMB received support from the NIH/NCATS, CTSA UL1TR000439, Cleveland, Ohio.
Genetics