Early onset or syndromic epilepsy
Gene: SEMA6BComment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus.
Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.Created: 1 Mar 2023, 3:32 p.m. | Last Modified: 1 Mar 2023, 3:32 p.m.
Panel Version: 3.93
Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus.
Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.Created: 1 Mar 2023, 3:32 p.m. | Last Modified: 1 Mar 2023, 3:32 p.m.
Panel Version: 3.92
Comment on publications: PMID:35604360 reported new unrelated cases identified with heterozygous variants in SEMA6B. Out of 16 patients referred for ID clinic, 10 of them had epilepsy or myoclonus.
Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.Created: 1 Mar 2023, 3:31 p.m. | Last Modified: 1 Mar 2023, 3:31 p.m.
Panel Version: 3.92
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.
Panel Version: 2.491
Hamanaka et al 2020 - Only seen in 4 individuals in 3 unrelated cases - all truncating de novo variants in the last exon - escape from NMD. They observed statistically significant enrichment of DNVs in NMD regions of 346 DEE trios. Although epilepsy is an initial feature, not sure there is enough evidence to make green?Created: 31 Jan 2021, 8:32 p.m. | Last Modified: 31 Jan 2021, 8:32 p.m.
Panel Version: 2.281
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).Created: 20 Oct 2020, 2:11 p.m. | Last Modified: 20 Oct 2020, 2:11 p.m.
Panel Version: 2.186
Comment on list classification: Gene was added to panel and rated Green by Zornitza Stark. Sufficient cases with seizure phenotype in PMID:32169168 plus mouse model. Not yet associated with a disorder in G2P but relevant OMIM phenotype. Therefore updated rating from Grey to Green.Created: 1 Jun 2020, 4:09 p.m. | Last Modified: 1 Jun 2020, 4:10 p.m.
Panel Version: 2.80
Comment on mode of pathogenicity: The authors of PMID:32169168 suggest a dominant-negative or gain-of-function effect rather than haploinsufficiency.Created: 1 Jun 2020, 4:08 p.m. | Last Modified: 1 Jun 2020, 4:08 p.m.
Panel Version: 2.79
PMID:32169168. In 4 unrelated patients (2 Japanese, 1 Israeli and 1 Malaysian) with progressive myoclonic epilepsy, Hamanaka et al. (2020) identified de novo heterozygous frameshift mutations in the last exon of the SEMA6B gene. Variants were predicted to result in truncated proteins. Truncating variants in this region of the gene were not observed in the gnomAD database, although truncating variants in other regions of the gene were observed in gnomAD. The authors postulated a dominant-negative or gain-of-function effect rather than haploinsufficiency. In an animal model, the authors found that zebrafish with truncating sema6b variants were more susceptible to seizures.Created: 1 Jun 2020, 4:07 p.m. | Last Modified: 1 Jun 2020, 4:08 p.m.
Panel Version: 2.78
Five individuals from unrelated families reported with de novo variants in the last exon, escaping NMD.
Sources: LiteratureCreated: 20 Apr 2020, 2:40 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Progressive myoclonic epilepsy
Publications
Publications for gene: SEMA6B were set to 32169168; 35604360
Publications for gene: SEMA6B were set to 32169168; 35604360
Publications for gene: SEMA6B were set to 32169168
Tag for-review was removed from gene: SEMA6B.
Source Expert Review Green was added to SEMA6B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: SEMA6B were changed from Epilepsy, progressive myoclonic, 11, 618876 to Epilepsy, progressive myoclonic, 11 OMIM:618876
Gene: sema6b has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: SEMA6B.
Gene: sema6b has been classified as Green List (High Evidence).
Mode of pathogenicity for gene: SEMA6B was changed from None to Other
Phenotypes for gene: SEMA6B were changed from Progressive myoclonic epilepsy to Epilepsy, progressive myoclonic, 11, 618876
gene: SEMA6B was added gene: SEMA6B was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SEMA6B were set to 32169168 Phenotypes for gene: SEMA6B were set to Progressive myoclonic epilepsy Review for gene: SEMA6B was set to GREEN