Researchers have discovered that mutations in the CD99L2 gene cause X-linked spastic ataxia, a rare movement disorder. The finding came from analysis of 2,811 patients with conditions affecting coordination and muscle control. The study was published in Nature Communications.
Scientists at Ruhr University Bochum and in Tübingen conducted genome-wide genetic analysis combined with cell experiments. They showed that CD99L2, previously known only for immune system functions, also supports communication between nerve cells by activating the CAPN1 protein.
"Disease-causing variants lead to disrupted production of the CD99L2 protein in the cell and prevent its interaction with CAPN1," said Dr. Jonasz Weber. Patients' cells displayed specific disruptions of synaptic processes, the researchers reported.
The work highlights the importance of pairing genetic diagnostics with functional studies. "Our results show that genetic diagnostics and functional neuroscience are not mutually exclusive areas," Weber added.
The discovery improves prospects for genetic diagnosis of rare movement disorders and provides new details on mechanisms of neurodegeneration.
