Genetic Epilepsy

Gene: UNC13B

Red List (low evidence)

Comment when marking as ready: Agree data is conflicting esp regarding MOI, and evidence for pathogenicity of several of the variants is limited.

Created: 5 Oct 2021, 10:43 a.m. | Last Modified: 5 Oct 2021, 10:43 a.m.

Panel Version: 0.1261

Red List (low evidence)

No OMIM human disease association. Gene encodes a presynaptic protein Munc13-2 highly expressed in the brain (predominantly cerebral cortex).

Variant interpretation data in human epilepsy cohort somewhat conflicting and restricted to a single study. Wang et al, Brain, 2021 - trio-based whole-exome sequencing identified UNC13B in 12 individuals affected by partial epilepsy and/or febrile seizures from 8 unrelated families. Identified:
x1 de novo nonsense variant, absent in gnomad, damaging in silicos
x1 de novo splice site, absent in gnomad, damaging in silicos
x1 splice site variant present in unaffected mother (low frequency in gnomad)
x2 compound het in one individual - more severe phenotype postulated (x1 variant present in contro cohortl, the other variant present in low frequency in gnomad)
x1 missense variant - in Han Chinese major depressive disorders study, not in gnomad
x1 missense variant - highly conserved residue, not in gnomad
x2 other missense variant - highly conserved residue, low frequency in gnomad
Latter 4 missense variants cosegregated with affected individuals in the families

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

De novo UNC13B variants previously reported in bipolar disorder and autism spectrum disorder
Sources: Expert list, Literature

Created: 5 Oct 2021, 9:39 a.m. | Last Modified: 5 Oct 2021, 9:42 a.m.

Panel Version: 0.1260

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy

Publications

• 33876820