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| Hereditary Spastic Paraplegia - paediatric v1.81 | PNPLA8 |
Chirag Patel gene: PNPLA8 was added gene: PNPLA8 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPLA8 were set to PMID: 39082157 Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases Review for gene: PNPLA8 was set to GREEN gene: PNPLA8 was marked as current diagnostic Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 15/23 individuals (info available) had spasticity (onset in early childhood). Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. Sources: Literature |
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| Hereditary Spastic Paraplegia - paediatric v1.74 | TUBA4A |
Bryony Thompson gene: TUBA4A was added gene: TUBA4A was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TUBA4A were set to 38884572; 37418012 Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related Mode of pathogenicity for gene: TUBA4A was set to Other Review for gene: TUBA4A was set to GREEN Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease. PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo. Sources: Literature |
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| Hereditary Spastic Paraplegia - paediatric v0.171 | SLC19A3 | Zornitza Stark Phenotypes for gene: SLC19A3 were changed from Biotin-thiamine-responsive basal ganglia disease to Biotin-thiamine-responsive basal ganglia disease, MIM#607483 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.127 | GAN | Zornitza Stark Marked gene: GAN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.127 | GAN | Zornitza Stark Gene: gan has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.127 | GAN | Zornitza Stark Phenotypes for gene: GAN were changed from Giant axonal neuropathy to Giant axonal neuropathy-1, MIM# 256850 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.126 | GAN | Zornitza Stark Publications for gene: GAN were set to 26381321 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.125 | GAN | Zornitza Stark reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062483; Phenotypes: Giant axonal neuropathy-1, MIM# 256850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Spastic Paraplegia - paediatric v0.0 | SLC19A3 |
Bryony Thompson gene: SLC19A3 was added gene: SLC19A3 was added to Hereditary Spastic Paraplegia - paediatric_RMH. Sources: Expert Review Red,Royal Melbourne Hospital Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC19A3 were set to Biotin-thiamine-responsive basal ganglia disease |
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| Hereditary Spastic Paraplegia - paediatric v0.0 | GAN |
Bryony Thompson gene: GAN was added gene: GAN was added to Hereditary Spastic Paraplegia - paediatric_RMH. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: GAN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GAN were set to 26381321 Phenotypes for gene: GAN were set to Giant axonal neuropathy |
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