Adult onset hereditary spastic paraplegia
Gene: SPTAN1
The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 5:08 p.m. | Last Modified: 10 Oct 2023, 5:08 p.m.
Panel Version: 3.19
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on classification: This gene should be rated Green as there are several unrelated cases (many more than three cases identified with different variants) reported with spastic paraplegia and supported by functional studies. Both autosomal dominant and autosomal recessive variants of this gene are implicated in spastic paraplegia and at least three cases are reported for both disorders.
Autosomal dominant disorder:
OMIM reports Developmental and epileptic encephalopathy 5 (OMIM #613477) as a phenotype for SPTAN1 variants. Spastic quadriplegia is one of the clinical manifestations that has been reported as part of this phenotype.
Two of three patients identified with SPTAN1 variants in PMID:20493457 were reported with spastic quadriplegia, while it has also been reported in one year old male from PMID:22656320 and two patients from PMID:18065176. Out of 22 patients from 14 families identified with SPTAN1 variants in PMID:35150594, fifteen patients from seven families displaying p.Arg19Trp variant were reported with hereditary spastic paraplegia with age of onset ranging from congenital to adolescence, 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 (three families) were presented with complex HA/HSP, two were presented with complex HSP and one with pure HSP.
Autosomal recessive disorder:
PMID:31515523 reported two cases of juvenile/ adult-onset spastic paraplegia caused by compound heterozygous variants (p.Ala858Ser/ p.Ala1428Gly & p.Ala858Ser/ Met2330Ile). PMID:34526651 reported a female patient with juvenile/ adult-onset spastic paraplegia and was identified with homozygous missense variant p.Ile1388Val.
Sources: LiteratureCreated: 6 Feb 2023, 3:23 p.m. | Last Modified: 6 Feb 2023, 5:59 p.m.
Panel Version: 2.9
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064
Publications
Tag Q1_23_promote_green was removed from gene: SPTAN1.
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)
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
Mode of inheritance for gene: SPTAN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPTAN1 were set to 18065176; 20493457; 22656320; 35150594; 36331550
Tag Q1_23_promote_green tag was added to gene: SPTAN1.
Gene: sptan1 has been classified as Amber List (Moderate Evidence).
gene: SPTAN1 was added gene: SPTAN1 was added to Hereditary spastic paraplegia - adult onset. Sources: Literature Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTAN1 were set to 18065176; 20493457; 22656320; 35150594; 36331550 Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5, OMIM:613477; Cerebellar ataxia, MONDO:0000437; Hereditary spastic paraplegia, MONDO:0019064 Review for gene: SPTAN1 was set to GREEN