Brain. 2021 Apr 20:awab164. doi: 10.1093/brain/awab164. Online ahead of print.
UNC13B variants associated with partial epilepsy with favourable outcome.
Wang J(, Qiao JD, Liu XR, Liu DT, Chen YH, Wu Y, Sun Y, Yu J, Ren RN, Mei Z, Liu YX, Shi YW, Jiang M, Lin SM, He N, Li B, Bian WJ, Li BM(, Yi YH, Su T, Liu HK, Gu WY, Liao WP; China Epilepsy Gene 1.0 Project.
From the abstract:
"The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein ... In this study we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy ... UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. ... The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant, and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database. Computational modeling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiologic recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results suggest that UNC13B is potentially associated with epilepsy. ..."
DOI: 10.1093/brain/awab164
PMID: 33876820
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