Parkinson's chromosome deletion linked to other genetic disorders

Researchers, led by BRC-supported Professor Nicholas Wood, UCL Institute of Neurology, have made a breakthrough in their understanding of Parkinson’s disease after they discovered a chromosome deletion linked to Parkinson’s disease and other genetic disorders.This study analysed multiple datasets, including significant contribution from UKPD study and the IPDGC consortium, both had received funding from The Wellcome Trust/MRC. This study found people with Parkinson’s disease had a piece of DNA missing from chromosome 22q. This particular ‘chromosome deletion’ has up until now normally been associated with DiGeorge syndrome, a genetic disorder usually noticeable at birth that can cause heart defects, problems with the mouth, feeding and hearing, and multiple other diseases.

“Our findings suggest there may be some Parkinson’s patients who also have undiagnosed DiGeorge disease. Interestingly, this deletion has also been reported in schizophrenia which, like Parkinson’s, involves dopamine signalling. The potential links and common pathophysiological mechanisms are very exciting indeed.” Professor Wood

The researchers studied large data sets from genome-wide association studies to find out more about rare copy number variants (CNVs) in Parkinson’s disease. CNVs refer to the duplications or deletions of genomic sequences and studies have linked common CNVs to a higher risk of developing several disorders, including schizophrenia and autism. Previous studies have shown common CNVs do not appear to play a role in Parkinson’s disease. This study, published in The Lancet Neurology, looked at whether rare CNVs, such as the deletion in chromosome 22q, could.

"This association of Parkinson’s disease with chromosomal 22q deletion highlights the clinical significance in identifying deletion carriers among patients with Parkinson’s disease, particular patients that have younger age of onset. The study found those Parkinson’s disease patients with the missing piece of chromosomal had multiple accompanying medical problems that warrant clinical attention, including medication-induced side effects, psychiatric and cognitive problems, and other undiagnosed congenital and biochemical abnormalities." Dr Mok, first author, Department of Molecular Neuroscience, UCL Institute of Neurology

Further information:

• Mok K et al. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data. Lancet Neurology 2016, Volume 15, No. 6, p585–596. DOI: http://dx.doi.org/10.1016/S1474-4422(16)00071-5
• Professor Wood's academic profile
• Dr Mok's academic profile
• NIHR UCLH BRC website

Image: Genomic location of the 22q11.2 deletions found in the eight patients with Parkinson's disease and location of the low copy repeat regions