Hereditary Spastic Paraplegia - adult onset
Gene: ATL1EnsemblGeneIds (GRCh38): ENSG00000198513
EnsemblGeneIds (GRCh37): ENSG00000198513
OMIM: 606439, Gene2Phenotype
ATL1 is in 8 panels
3 reviews
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
Age of onset is variable (first, second, third decade).
Created: 11 May 2020, 11:12 a.m. | Last Modified: 15 Mar 2021, 11:31 p.m.
Panel Version: 0.54
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hereditary sensory neuropathy type ID, MIM 613708; Spastic paraplegia 3A, MIM 182600; Hereditary spastic paraplegia, AR
Publications
Teresa Zhao (Victorian Clinical Genetics Services)
No clear genotype-phenotype correlation. However, most SPG3A exhibits an early onset, and most mutations are missense mutations (PMID: 28396731).
Hom nonsense (PMID: 24473461) and hom missense (PMID: 26888483) were reported for AR HSP.
Disease mechanism (PTC variants): LoF
LoF: hom nonsense (p.R217* in alt transcript) identified in a consanguineous family, and carriers are healthy (PMID: 26888483).
Disease mechanism (missense variants):
Dominant negative: Mutant atlastin-1 protein functionally impair the atlastin-1 oligomer by binding to WT protein —> reduce GTPase activity (PMID: 16537571) —> cause HSP3A
LoF: Variants fall outside of the GTPase related motifs or the conserved motifs is linked to neuropathy, suggesting an alternative mechanism is used apart from dom-neg (PMID: 28396731) —> cause HSN1D
More than 90% of the mutations were located in exon 4, 7, 8 and 12 (PMID: 16401858)Created: 11 May 2020, 10:27 a.m. | Last Modified: 11 May 2020, 10:27 a.m.
Panel Version: 0.20
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hereditary sensory neuropathy type ID, MIM 613708; Spastic paraplegia 3A, MIM 182600; Hereditary spastic paraplegia, AR
Publications
Mode of pathogenicity
Other
Bryony Thompson (Royal Melbourne Hospital)
Usually shows early age at onset.
Sources: Expert listCreated: 17 Apr 2020, 6:50 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spastic paraplegia 3A, autosomal dominant MIM#182600
Details
- Mode of Inheritance
- BOTH monoallelic and biallelic, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- Expert list
- Royal Melbourne Hospital
- Phenotypes
-
- Spastic paraplegia 3A, MIM 182600
- Hereditary spastic paraplegia, AR
- OMIM
- 606439
- Clinvar variants
- Variants in ATL1
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: atl1 has been classified as Green List (High Evidence).
Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Phenotypes for gene: ATL1 were changed from Spastic paraplegia 3A, 182600 autosomal dominant; Spastic Paraplegia, Dominant; Neuropathy, hereditary sensory, type ID, 613708 to Spastic paraplegia 3A, MIM 182600; Hereditary spastic paraplegia, AR
Set publications
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Publications for gene: ATL1 were set to
Set mode of inheritance
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Mode of inheritance for gene: ATL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Created, Added New Source, Set mode of inheritance, Set Phenotypes
Bryony Thompson (Royal Melbourne Hospital)gene: ATL1 was added gene: ATL1 was added to Hereditary Spastic Paraplegia - adult onset_RMH. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: ATL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ATL1 were set to Spastic paraplegia 3A, 182600 autosomal dominant; Spastic Paraplegia, Dominant; Neuropathy, hereditary sensory, type ID, 613708