Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxia - PubMed
8 days ago
- #genetics
- #spastic-ataxia
- #neurodegeneration
- Loss-of-function variants in CD99L2 cause X-linked spastic ataxia.
- Exome sequencing provides genetic diagnoses in 19.3% of cases, with genome analysis increasing yield by 7.5%.
- CD99L2 is a transmembrane protein that activates CAPN1, a calcium-dependent protease.
- Ablation of CD99L2 domains disrupts its interaction with CAPN1 and leads to mislocalization.
- Transcriptome analysis in patient-derived fibroblasts shows synaptic function disturbances.
- Impaired CAPN1 activation and downstream neuronal pathway dysregulation likely cause neurodegeneration.