The phenotypic spectrum associated with loss-of-function variants in monogenic epilepsy genes in the general population

Smuk, Victoria, Lopez-Rivera, Javier A., Leu, Costin and Lal, Dennis . The phenotypic spectrum associated with loss-of-function variants in monogenic epilepsy genes in the general population. Eur. J. Hum. Genet.. LONDON: SPRINGERNATURE. ISSN 1476-5438

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DOI:10.1038/s41431-022-01211-w

Abstract

Variants in monogenic epilepsy genes can cause phenotypes of varying severity. For example, pathogenic variants in the SCN1A gene can cause the severe, sporadic, and drug-resistant Dravet syndrome or the milder familiar GEFS + syndrome. We hypothesized that coding variants in epilepsy-associated genes could lead to other disease-related phenotypes in the general population. We selected 127 established monogenic epilepsy genes and explored rare loss-of-function (LoF) variant associations with 3700 phenotypes across 281,850 individuals from the UK Biobank with whole-exome sequencing data. For 5.5% of epilepsy genes, we found significant associations of LoF variants with non-epilepsy phenotypes, mostly related to mental health. These findings suggest that LoF variants in epilepsy genes are associated with neurological or psychiatric phenotypes in the general population. The evidence provided may warrant further research and genetic screening of patients with atypical presentation and inform clinical care of comorbid disorders in individuals with monogenic epilepsy forms.

Item Type:

Journal Article

Creators:

Creators	Email	ORCID	ORCID Put Code
Smuk, Victoria	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Lopez-Rivera, Javier A.	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Leu, Costin	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Lal, Dennis	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED