Despite modern high-throughput sequencing, the genetic causes of most rare movement disorders remain unknown. The research team from Bochum and Tübingen has solved one piece of the puzzle. Researchers tested 2,811 patients with ataxia, hereditary spastic paraplegia, and dystonia to identify genetic mutations that cause the disease. CD99L2 As a cause of X-linked spastic ataxia. The findings were published in the journal Nature Communications on February 14, 2026.
cooperation partner
Genetic analysis of a large patient cohort was performed in Tübingen under the supervision of Dr. Tobias Haack. The functional characterization of the newly identified disease genes was led by Dr. Jonas Weber’s team at the Department of Human Genetics at Ruhr University Bochum.
Genes with previously unknown neurological functions
CD99L2 was primarily known for its function in the immune system, but its role in the nervous system had not been previously described. Only by combining genome-wide analysis and cell biological experiments, the researchers were able to show that this gene plays an important role in neural signaling pathways.
Researchers from Bochum have demonstrated that the protein encodes. CD99L2 It acts as an activating partner for the calcium-dependent protease CAPN1, a known disease protein in spastic paraplegia and ataxia. “Disease-causing variants disrupt the production of the CD99L2 protein in cells and prevent it from interacting with CAPN1,” explains Dr. Jonasz Weber. “We also observed a specific disruption of synaptic processes in patients’ cells.” Reduced CAPN1 activation and the resulting dysregulation of neural signaling pathways is a plausible explanation for the observed symptoms.
Our results demonstrate that genetic diagnostics and functional neuroscience are not mutually exclusive fields. Only when both fields work closely together can reliable disease mechanisms be derived from genetic variations. ”
Dr. Jonasz Weber, Department of Human Genetics, Ruhr-University Bochum
identification of CD99L2 As a new disease gene, it not only improves genetic diagnosis of rare movement disorders but also provides new insights into the underlying neurodegenerative mechanisms.
spastic ataxia
Spastic ataxia refers to a rare neurodegenerative disease in which impaired motor coordination (ataxia) is combined with spastic paralysis. Symptoms occur due to involvement of the cerebellar and motor pathways of the central nervous system. The onset and course of the disease depends on the genetic cause.
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Reference magazines:
Menden, B. Others. (2026). Loss-of-function mutants of the CAPN1 activator CD99L2 cause X-linked spastic ataxia. nature communications. DOI: 10.1038/s41467-026-69337-9. https://www.nature.com/articles/s41467-026-69337-9
