Early onset or syndromic epilepsy
Gene: KLHL20This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:36214804 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag.Created: 16 Oct 2023, 7:34 p.m. | Last Modified: 16 Oct 2023, 7:34 p.m.
Panel Version: 4.118
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, noon | Last Modified: 11 Oct 2023, noon
Panel Version: 4.110
Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel review.
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Sleyp et al. 2022 (PMID: 36214804) reported on 14 patients with de novo missense variants who all presented with mild to severe ID, seizures, ASD, hyperactivity, and dysmorphic facial features. One variant (c.1069G>A, p.Gly357Arg) was recurrent in 11/14 cases but all variants clustered in the Kelch-type β-propeller domain (substrate binding surface) of the KLHL20 protein. No functional studies were performed but given the overlap in clinical presentation observed in patients with the same recurrent variant but also multiple different variants, its worth including as diagnostic-grade.Created: 19 Dec 2022, 3:24 p.m. | Last Modified: 19 Dec 2022, 3:24 p.m.
Panel Version: 3.11
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
14 cases with mostly recurrent missense variant in this gene is reported.
Sources: LiteratureCreated: 8 Dec 2022, 11:17 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag gene-checked tag was added to gene: KLHL20.
Tag Q4_22_promote_green was removed from gene: KLHL20.
Source NHS GMS was added to KLHL20. Source Expert Review Green was added to KLHL20. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: klhl20 has been classified as Amber List (Moderate Evidence).
Tag Q4_22_promote_green tag was added to gene: KLHL20.
gene: KLHL20 was added gene: KLHL20 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: KLHL20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLHL20 were set to 36214804 Phenotypes for gene: KLHL20 were set to developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder Mode of pathogenicity for gene: KLHL20 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: KLHL20 was set to GREEN