Early onset or syndromic epilepsy
Gene: SNIP1
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 9:39 a.m. | Last Modified: 1 Feb 2023, 9:39 a.m.
Panel Version: 3.29
Ammous et al, 2021: extensive genetic studies and clinical findings of a complex inherited AR neurodevelopmental disorder in 35 individuals asociated with a SNIP1 c.1097A>G p.(Glu366Gly) variant present at a high frequency in the Amish community. Cardinal clinical features include hypotonia, global developmental delay, intellectula disability, seizures and a characteristic craniofacial appearance.
35 of 51 idenitifed individuals from 21 interrelated old order Amish families, including new findings for two aff individuals prev published by Puffenberger et al 2012 - 22279524.
Supp data - SNIP1 variant idenitifed p.Arg111Cys - classed as pathogenic - no other information.Created: 11 Nov 2022, 3:14 p.m. | Last Modified: 11 Nov 2022, 3:14 p.m.
Panel Version: 2.603
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Updating tags to be Q3_22_expert_review and Q3_22_rating so that gene is included in the next GMS report (Oct 2022)Created: 6 Oct 2022, 1:40 p.m. | Last Modified: 6 Oct 2022, 1:40 p.m.
Panel Version: 2.597
As far as I can see only 3 Amish patients reported with same homozygous variant, founder effect.Created: 27 Feb 2020, 3:37 a.m. | Last Modified: 27 Feb 2020, 3:37 a.m.
Panel Version: 2.3
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Psychomotor retardation, epilepsy, and craniofacial dysmorphism, 614501
Publications
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: Alison Callaway and John Taylor. Suggested gene rating: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Psychomotor retardation, epilepsy, and craniofacial dysmorphism, 614501
Publications
Q4_21_expert_review tag has been added to this gene. Helen Brittain (Genomics England Clinical Fellow) has suggested that the rating of this gene should be considered by TEWG oversight committee, to decide whether this gene could be green, as the disease association has only been associated with a the founder variant.Created: 28 Oct 2021, 3:16 p.m. | Last Modified: 28 Oct 2021, 3:16 p.m.
Panel Version: 2.452
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. A single (founder) variant NM_024700.4:c.1097A>G, p.(Glu366Gly) has been reported in over 30 cases of Psychomotor retardation, epilepsy, and craniofacial dysmorphism OMIM:614501 in the Amish community (PMIDs: 22279524; 34570759). Cases are homozygous for this variant and unaffected members of the families are heterozygous or wt. Overexpression of the equivalent mouse variant in mouse inner medullary collecting duct cells, resulted in a more aggregated appearance in the nucleus compared to wildtype. The variant protein maybe unstable as Western blots showed reduced levels of the variant protein (PMID: 22279524). Whole transcriptomic analysis of patient blood was performed in PMID: 34570759. This revealed 11 upregulated and 32 downregulated genes, of which 24 had previously been associated with neurological disease.Created: 12 Oct 2021, 5:14 p.m. | Last Modified: 12 Oct 2021, 5:14 p.m.
Panel Version: 2.444
Gene originally listed on the Intellectual disability panel V2.42.
Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. One variant identified in 3 Amish cases of Psychomotor retardation, epilepsy, and craniofacial dysmorphism 614501, supportive functional studies were presented (pmid 22279524)Created: 21 Jun 2018, 11:09 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Psychomotor retardation, epilepsy, and craniofacial dysmorphism 614501
Publications
Tag Q3_22_rating was removed from gene: SNIP1. Tag Q3_22_expert_review was removed from gene: SNIP1.
Source Expert Review Green was added to SNIP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: SNIP1 were set to 22279524; 34570759
Tag Q4_21_expert_review was removed from gene: SNIP1. Tag Q3_22_rating tag was added to gene: SNIP1. Tag Q3_22_expert_review tag was added to gene: SNIP1.
Tag Q4_21_expert_review tag was added to gene: SNIP1.
Tag founder-effect tag was added to gene: SNIP1.
Phenotypes for gene: SNIP1 were changed from Psychomotor retardation, epilepsy, and craniofacial dysmorphism 614501 to Psychomotor retardation, epilepsy, and craniofacial dysmorphism OMIM:614501; psychomotor retardation, epilepsy, and craniofacial dysmorphism MONDO:0013787
Publications for gene: SNIP1 were set to 22279524
Source Wessex and West Midlands GLH was added to SNIP1.
Source NHS GMS was added to SNIP1.
Sarah Leigh: Gene originally listed on the
Gene: snip1 has been classified as Amber List (Moderate Evidence).
Gene: snip1 has been classified as Amber List (Moderate Evidence).
SNIP1 was added to Genetic Epilepsy Syndromes panel. Sources: Literature
SNIP1 was created by Sarah Leigh