Scientists at the University of Birmingham have discovered genetic mutations that cause a rare childhood neurological disorder that could also have important implications for our understanding of Parkinson’s disease.
Led by Professor Eamonn Maher and Dr Manju Kurian, the Birmingham team conducted detailed genetic sequencing in two families who had children diagnosed with infantile parkinsonism-dystonia (IPD) - a rare, recently discovered, genetic condition that produces symptoms similar to Parkinson’s disease in children.
The results of the investigation, published in the Journal of Clinical Investigation, identified mutations in the dopamine transporter gene (SLC6A3) which severely affects the transport of dopamine in the nervous system. This is the first time a loss-of function mutation of the dopamine transporter has been identified. Variations in the dopamine transporter have been implicated in a number of diseases including ADHD, schizophrenia, and bipolar disorder. However, identification of the molecular basis of IPD suggests that the dopamine transporter could also be a candidate gene for other movement disorders associated with Parkinsonism and other dystonic features,
Dr Kurian says: “The fact the mutations occurs in a gene which plays an important role in dopamine transport opens up a wide range of possibilities for studying more common diseases. The SLC6A3 gene has been suggested as a candidate for conditions as varied as Parkinson’s disease and ADHD, but this is the first time we have seen changes in the gene definitely linked to Parkinson’s disease-like symptoms.
“This opens up a rich seam of research and we will continue work to identify the clinical symptoms of IPD and to look at the significance of this mutation in other similar conditions.”
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease and affects approximately 1% of the population over 50 years of age.
Fellow researcher, Professor Eamonn Maher adds: “Because IPD is a newly identified condition, detailed genetic analysis had not been conducted before. The symptoms can lead to it being confused with cerebral palsy. From our perspective it was hugely important to find a genetic mutation that will allow better identification of IPD.”
The discovery of the gene for infantile parkinsonism-dystonia (IPD) has also already led to the diagnosis of a further nine new cases, which had previously been misidentified as cerebral palsy.
Further functional studies revealed that both gene defects severely reduced the levels of DAT, which plays an important role in dopamine transportation. Dopamine has many functions in the brain, including important roles in behaviour, cognition and voluntary movement. In mice however, mutations to the DAT gene produces prominent hyperactivity rather than Parkinsonian symptoms.
The research was carried out in collaboration with colleagues from New York, Sheffield, Bristol and London and is supported by New Life, Action Medical Research, the Wellcome Trust, WellChild, and the NIH.
Further Media Information
Dr Manju Kurian is available for interview, please contact Anna Mitchell on 0121 414 6029 / 07920 593946.