Activity
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| Childhood onset hereditary spastic paraplegia v8.16 | TBCB | Arina Puzriakova Classified gene: TBCB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v8.16 | TBCB | Arina Puzriakova Added comment: Comment on list classification: Rating Amber following consultation with the Genomics England Clinical Team. Some functional data that indicates disruption of the gene, however this does not provide conclusive support for pathogenicity of the founder variant. Additional functional evidence or corroborative cases would allow verification of this gene-disease association and future review of the classification on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v8.16 | TBCB | Arina Puzriakova Gene: tbcb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v8.13 | TBCB |
Arina Puzriakova gene: TBCB was added gene: TBCB was added to Childhood onset hereditary spastic paraplegia. Sources: Literature watchlist, founder-effect tags were added to gene: TBCB. Mode of inheritance for gene: TBCB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBCB were set to 40856104 Phenotypes for gene: TBCB were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: TBCB was set to AMBER Added comment: PMID: 40856104 (2025) - 10 individuals from 8 unrelated families of Ashkenazi Jewish descent with the same homozygous founder variant (c.589T>A, p.(Tyr197Asn)) in TBCB. Affected individuals presented during infancy with motor or speech delays and developed late-childhood-onset spastic paraparesis (onset around 9-12 years old), global developmental delay (formal assessment done in 5 individuals, indicating mild ID), and autism spectrum. Brain MRI showed corpus collosum thinning in 3, and decreased white matter in 2. The c.589T>A (GRCh38: 19-36125492-T-A) variant has an AF of 0.006485 in the Ashkenazi Jewish population in gnomAD v4 with 0 homozygotes. Classified as VUS in ClinVar based on 1 submission. TBCB protein levels were reduced in patient fibroblasts. Drosophila melanogaster model showed reduced survival and impaired climbing ability. Sources: Literature |
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