Even with today’s fast DNA tests, many rare movement problems still have unknown causes. A German research team has now found an important clue.
By studying 2,811 people who had ataxia, hereditary spastic paraplegia, or dystonia, the scientists discovered that damaging changes in a gene called CD99L2 cause a condition known as X‑linked spastic ataxia.
The finding was shared in a scientific journal. It helps explain a mystery disorder and shows how some brain‑degenerative diseases may start.
CD99L2 Linked to a Rare Brain Disease
Before this work, CD99L2 was mostly known for helping the immune system. No role in the brain had been proved.
Using large‑scale genetic screens and lab experiments with cells, the team showed that CD99L2 also helps nerve cells talk to each other. The gene is key for normal brain signaling.
How the Gene Works in Brain Cells
Researchers at Ruhr University Bochum found that the CD99L2 protein partners with another protein called CAPN1. CAPN1 is a calcium‑dependent enzyme already linked to hereditary spastic paraplegia and ataxia.
"When harmful variants appear, the CD99L2 protein is not made correctly and cannot join with CAPN1," said Dr. Jonasz Weber. "Patient cells also showed problems with the connections between neurons."
Without proper CD99L2, CAPN1 is less active. This weakens important signaling pathways in brain cells, which likely leads to the movement problems seen in patients.
Uniting Genetics and Brain Science
The study shows that pairing genetic testing with experiments that reveal how genes work inside cells is powerful.
"Genetic diagnosis and functional neuroscience go hand in hand," Weber explained. "When they work together, we can understand how a genetic change causes disease."
Knowing that CD99L2 causes disease can improve genetic testing for people with rare movement disorders and gives scientists new clues about how neurodegeneration happens.
What Is Spastic Ataxia?
Spastic ataxia describes a group of rare brain disorders that combine poor movement coordination (ataxia) with stiff, spastic muscles. Damage to the cerebellum and motor pathways in the central nervous system creates these symptoms.
The age when symptoms start and how quickly they get worse can differ a lot, depending on the gene involved.
The large genetic study was organized in Tübingen under Dr. Tobias Haack. Functional experiments on the new disease gene were led by Dr. Jonasz Weber and his team at the Department of Human Genetics, Ruhr University Bochum.