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| Mendeliome v1.4162 | SPTSSA | Zornitza Stark Publications for gene: SPTSSA were set to 36718090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.4161 | SPTSSA | Zornitza Stark changed review comment from: Another individual with heterozygous de novo missense c.152C>T (p.Thr51Ile) reported, same variant, no change in rating.; to: Another individual with heterozygous de novo missense c.152C>T (p.Thr51Ile) reported, same variant, no change in rating, AMBER for both MOI. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.4161 | SPTSSA | Zornitza Stark edited their review of gene: SPTSSA: Added comment: Another individual with heterozygous de novo missense c.152C>T (p.Thr51Ile) reported, same variant, no change in rating.; Changed publications: 40533086 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.943 | SPTSSA | Zornitza Stark Phenotypes for gene: SPTSSA were changed from complex hereditary spastic paraplegia, MONDO:0015150 to Spastic paraplegia 90B, autosomal recessive , MIM# 620417; Spastic paraplegia 90A, autosomal dominant, MIM# 620416 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.942 | SPTSSA | Zornitza Stark reviewed gene: SPTSSA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 90B, autosomal recessive , MIM# 620417, Spastic paraplegia 90A, autosomal dominant, MIM# 620416; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.649 | SPTSSA | Seb Lunke Marked gene: SPTSSA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.649 | SPTSSA | Seb Lunke Gene: sptssa has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.649 | SPTSSA | Seb Lunke Classified gene: SPTSSA as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.649 | SPTSSA | Seb Lunke Added comment: Comment on list classification: Three individuals but only two variants with different inheritance. Amber despite functional data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.649 | SPTSSA | Seb Lunke Gene: sptssa has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.648 | SPTSSA |
Seb Lunke gene: SPTSSA was added gene: SPTSSA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SPTSSA was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SPTSSA were set to 36718090 Phenotypes for gene: SPTSSA were set to complex hereditary spastic paraplegia, MONDO:0015150 Review for gene: SPTSSA was set to AMBER Added comment: Three unrelated individuals with common neurological features of developmental delay, progressive motor impairment, progressive lower extremity spasticity, and epileptiform activity or seizures. Other additional features varied. Two of the individuals had the same de-novo missense, Thr51Ile, while the third was homozygous for a late truncating variant, Gln58AlafsTer10. The patient with the hom variant was described as less severe. Functional studies in fibroblasts showed dysregulation of the sphingolipid (SL) synthesis pathway, showing that both variants impair ORMDL regulation of the pathway leading to various levels of increased SL. Over expression of human SPTSSA was shown to lead to motor development in flies, rescued by expression of ORMDL for WT SPTSSA but not mutant SPTSSA. The de-novo missense were shown to impact regulation more than the hom truncation, while the truncated region was shown to previously to be important for ORMDL regulation. Mice with a hom KO of the functional equivalent sptssb had early onset ataxia and died prematurely, with evidence of axonic degeneration. Sources: Literature |
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