Recurrent KCNT2 missense variants affecting p.Arg190 result in a recognizable phenotype
AuthorsJackson, Adam; orcid: 0000-0002-3674-3960; email: email@example.com
Banka, Siddharth; orcid: 0000-0002-8527-2210
Stewart, Helen; orcid: 0000-0002-1196-3000
Genomics England Research Consortium
MetadataShow full item record
AbstractAbstract: KCNT2 variants resulting in substitutions affecting the Arg190 residue have been shown to cause epileptic encephalopathy and a recognizable facial gestalt. We report two additional individuals with intellectual disability, dysmorphic features, hypertrichosis, macrocephaly and the same de novo KCNT2 missense variants affecting the Arg190 residue as previously described. Notably, neither patient has epilepsy. Homology modeling of these missense variants revealed that they are likely to disrupt the stabilization of a closed channel conformation of KCNT2 resulting in a constitutively open state. This is the first report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy.
CitationAmerican Journal of Medical Genetics Part A
PublisherJohn Wiley & Sons, Inc.
DescriptionFrom Wiley via Jisc Publications Router
History: received 2021-01-05, rev-recd 2021-03-29, accepted 2021-05-05, pub-electronic 2021-06-01
Article version: VoR
Publication status: Published
Funder: National Institute for Health Research and NHS England
Funder: European Union's Horizon 2020 research and innovation program; Grant(s): 779257