Early onset or syndromic epilepsy
Gene: STXBP1The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, noon | Last Modified: 11 Oct 2023, noon
Panel Version: 4.110
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on mode of inheritance: Due to the report of biallelic STXBP1 variants in a family with encephalopathy, developmental delay, intellectual disability and epilepsy (PMID: 31855252), the mode of inheritance for this gene should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.Created: 28 Feb 2023, 3:43 p.m. | Last Modified: 28 Feb 2023, 3:43 p.m.
Panel Version: 3.86
PMID: 31855252 reports a homozygous STXBP1 variant (NM_001032221.6(STXBP1):c.1336C>T (p.Leu446Phe)) in two sisters with developmental and epileptic encephalopathy 4 (OMIM:612164). Their mother and unaffected sister were heterozygous for NM_001032221.6(STXBP1):c.1336C>T (p.Leu446Phe)(the father was deceased). Functional studies showed that this variant had a lesser effect on protein stability in comparison with the heterozygous variants previously reported. However, patch clamp recordings demonstrated that p.Leu446Phe causes a 2-fold increase in evoked
synaptic transmission, leading to the conclusion that this variant was having a gain-of-function effect.
Although the majority of STXBP1 variants are heterozygous, with a loss-of -function effect, the results published in PMID: 31855252, suggest that there maybe further complexity to mechanisms involved in the development of developmental and epileptic encephalopathy 4.
PMID: 35190816 used a computational approach, together with biomedical ontologies, to characterize phenotypic features in STXBP1-related disorders, such that groups of HPO terms could be associated with certain STXBP1 variants.Created: 28 Feb 2023, 3:37 p.m. | Last Modified: 28 Feb 2023, 3:37 p.m.
Panel Version: 3.85
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
Please note recent report of BIALLELIC variants in this gene causing EE through GoF in two families and consider changing mode of inheritance/pathogenicity and associated pipeline settings.Created: 21 Jan 2020, 10:31 a.m. | Last Modified: 21 Jan 2020, 10:31 a.m.
Panel Version: 2.0
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Epileptic encephalopathy, early infantile, 4, MIM#612164
Publications
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
AD Early infantile epileptic encephalopathy - lots of types of seizures reported in association with variants in this gene. Lots of reported variants on OMIM and HGMD Pro.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epileptic encephalopathy, early infantile, 612164
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 4
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 4
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 4
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: Monoallelic confirmed on G2P and OMIM. Not on the imprinted gene list.Created: 29 Jan 2016, 12:46 p.m.
Comment on list classification: Reviewers later agreed that this gene should be green. It is a confirmed DD gene for Epileptic encephalopathy.Created: 29 Jan 2016, 12:33 p.m.
Phenotypes for gene: STXBP1 were changed from Developmental and epileptic encephalopathy 4, OMIM:612164; developmental and epileptic encephalopathy, 4, MONDO:0012812 to Developmental and epileptic encephalopathy 4, OMIM:612164
Tag Q1_23_MOI was removed from gene: STXBP1.
Mode of inheritance for gene STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STXBP1 were set to 31855252; 18469812; 19557857
Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q1_23_MOI tag was added to gene: STXBP1.
Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4 to Developmental and epileptic encephalopathy 4, OMIM:612164; developmental and epileptic encephalopathy, 4, MONDO:0012812
Publications for gene: STXBP1 were set to Saitsu et al (2008) Nature Genet 40 (6): 782-788
Source Wessex and West Midlands GLH was added to STXBP1.
Source NHS GMS was added to STXBP1.
Ellen McDonagh: Comment on list classification
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to STXBP1. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to STXBP1. Panel: Genetic Epilepsy Syndromes
STXBP1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,UKGTN
STXBP1 was created by Sarah Leigh