Researchers discover gene mutation that causes chorea in childhood
14 April 2016
Mutations in a gene that helps brain cells communicate with one another can cause chorea in childhood, according to research led by UCL Institute of Neurology, published in the American Journal of Human Genetics.
The research team led by Professors Kailash Bhatia and Nicholas Wood sequenced the DNA of chorea cases without genetic diagnoses and found that mutations in the phosphodiesterase 10A (PDE10A) gene, which is highly expressed in neurons in the brain associated with neurological disorders like chorea, are a cause for this condition.
BRC supported Dr Mencacci, UCL Institute of Neurology, the first author of the paper, said: “In the genetically unsolved cases of chorea we found three patients with mutations in PDE10A. The patients’ clinical presentation was strikingly similar, including a fairly unique abnormal signal in the basal ganglia region of the brain. In this region a group of nuclei best known for their role in facilitating voluntary movement can be found.”
Chorea is a movement disorder and a feature of several inherited neurological disorders such as Huntington’s disease and Parkinson’s disease. It is characterised by brief, abrupt and unpredictable movements. Medications are available to help suppress chorea. However, this can often worsen cognitive effects or trigger psychiatric conditions.
The findings may enable researchers to develop therapy for chorea patients in the future by modulating the activity of the PDE10A gene. However more research is required first.
Dr Mencacci, UCL Institute of Neurology, said: “We found mutations in the PDE10A gene that can cause chorea, so we know this to be the right target. However we don’t yet know whether increasing or decreasing activity of PDE10A could help treat chorea.”
study was carried out jointly with Takeda Pharmaceutical Company Limited.
- Mencacci et al. De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions American Journal of Human Genetics (2016) Volume 98, Issue 4, p763–771. DOI:10.1016/j.ajhg.2016.02.015
- Dr Mencacci's academic profile
- UCLH BRC website
Image: MRI of patients with Dominant PDE10A mutations showing increased signal intensity within the striata