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| Hereditary Spastic Paraplegia - adult onset v0.54 | ATL1 |
Zornitza Stark changed review comment from: Age of onset is variable (first, second, third decade). 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); to: Age of onset is variable (first, second, third decade). |
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| Hereditary Spastic Paraplegia - adult onset v0.54 | ATL1 | Zornitza Stark Marked gene: ATL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - adult onset v0.54 | ATL1 | Zornitza Stark Gene: atl1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - adult onset v0.54 | ATL1 | Zornitza Stark 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - adult onset v0.53 | ATL1 | Zornitza Stark Publications for gene: ATL1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - adult onset v0.52 | ATL1 | Zornitza Stark Mode of inheritance for gene: ATL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - adult onset v0.51 | ATL1 |
Zornitza Stark changed review comment from: 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); to: Age of onset is variable (first, second, third decade). 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) |
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| Hereditary Spastic Paraplegia - adult onset v0.0 | ATL1 |
Bryony Thompson 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 |
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