Ataxia and cerebellar anomalies - narrow panel
Gene: SPTAN1EnsemblGeneIds (GRCh38): ENSG00000197694
EnsemblGeneIds (GRCh37): ENSG00000197694
OMIM: 182810, Gene2Phenotype
SPTAN1 is in 10 panels
3 reviews
Eleanor Williams (Genomics England Curator)
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 10:01 a.m. | Last Modified: 11 Oct 2023, 10:01 a.m.
Panel Version: 4.37
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on mode of inheritance: Although there are three unrelated cases reported with biallelic SPTAN1 variants and hereditary spastic paraplegia, they do not present with ataxia (PMID:31515523; PMID:34526651). Hence, the MOI should remain as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".Created: 17 Aug 2023, 8:55 a.m. | Last Modified: 17 Aug 2023, 8:55 a.m.
Panel Version: 4.29
Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) from multiple ethnicities reported with ataxia and was also supported by functional studies including results from mouse model.
One patient each was identified with SPTAN1 variants and was reported with ataxia from PMID:29050398 and PMID:30548380. Out of three patients identified with SPTAN1 variants and reported with Developmental and epileptic encephalopathy 5 in PMID:34590414, one patient had ataxia and another had mild ataxia. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, four unrelated patients displaying p.Lys2083del variant were reported with cerebellar ataxia, while three other patients displaying other variants (p.Arg1624Cys, p.Arg1098Cys & p.Gln2205Pro) displayed different extremes of spastic ataxia spectrum.
In PMID:36331550, authors carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Statistically significant enrichment of rare probably damaging SPTAN1 variants were identified in families with hereditary ataxia (HA) or spastic paraplegia (HSP). Out of 31 individuals identified with SPTAN1 variants, five (from three families) were presented with complex HA/HSP and two were presented with pure HA.
A 33-year old Korean woman identified with SPTAN1 variant was reported with cerebellar ataxia in PMID:36408834, being the first reported case of SPTAN1-related cerebellar ataxia.
In addition, a strain of C57BL/6J mice harbouring a single point mutation in Sptan1 (c.3293G > A/ p.Arg1098Gln) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis was reported in PMID:33790315. Homozygotes are embryonically lethal and heterozygotes develop a progressive ataxia.Created: 6 Feb 2023, 2:32 p.m. | Last Modified: 6 Feb 2023, 3:22 p.m.
Panel Version: 3.35
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Publications
Dmitrijs Rots (Children's Clinical University Hospital)
Two large cohorts (36331550; 35150594) described >30 cases with hereditary ataxia and a variant in SPTAN1.
Sources: LiteratureCreated: 15 Dec 2022, 11:48 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Ataxia; hereditary spastic paraplegia
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- NHS GMS
- Expert Review Green
- Phenotypes
-
- Developmental and epileptic encephalopathy 5, OMIM:613477
- Developmental delay with or without epilepsy, OMIM:620540
- Spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia, OMIM:620538
- OMIM
- 182810
- Clinvar variants
- Variants in SPTAN1
- Penetrance
- None
- Publications
- Panels with this gene
-
- Hereditary ataxia with onset in adulthood
- Intellectual disability
- Hereditary neuropathy or pain disorder
- Fetal anomalies
- DDG2P
- Adult onset hereditary spastic paraplegia
- Ataxia and cerebellar anomalies - narrow panel
- Distal myopathies
- Childhood onset hereditary spastic paraplegia
- Early onset or syndromic epilepsy
History Filter Activity
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277 to Developmental and epileptic encephalopathy 5, OMIM:613477; Developmental delay with or without epilepsy, OMIM:620540; Spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia, OMIM:620538
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q1_23_promote_green was removed from gene: SPTAN1.
Added New Source, Added New Source, Status Update
Achchuthan Shanmugasundram (Genomics England Curator)Source Expert Review Green was added to SPTAN1. Source NHS GMS was added to SPTAN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Set mode of inheritance
Achchuthan Shanmugasundram (Genomics England Curator)Mode of inheritance for gene: SPTAN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Set Phenotypes
Sarah Leigh (Genomics England Curator)Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064 to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: SPTAN1 were changed from Ataxia; hereditary spastic paraplegia to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Set publications
Achchuthan Shanmugasundram (Genomics England Curator)Publications for gene: SPTAN1 were set to 36331550; 35150594
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q1_23_promote_green tag was added to gene: SPTAN1.
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: sptan1 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Dmitrijs Rots (Children's Clinical University Hospital)gene: SPTAN1 was added gene: SPTAN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTAN1 were set to 36331550; 35150594 Phenotypes for gene: SPTAN1 were set to Ataxia; hereditary spastic paraplegia Review for gene: SPTAN1 was set to GREEN