Neuropathologists Dr. Rasmus Kiehl and Dr. Lili-Naz Hazrati of the Laboratory Medicine Program hold  “Tremor”, an image from a case of a patient with Parkinson’s Disease with a single “Lewy Body” as in their study. (Photo: UHN)

Researchers at the University Health Network have identified a previously unknown connection between Parkinson’s disease and a genetic mutation called 22q11.2 deletion syndrome.
The study, recently published in the JAMA Neurology journal, helps shine a new light on the effects this type of molecular change can have on the likelihood of that same patient developing Parkinson’s disease.
The research team includes Dr. Rasmus Kiehl and Dr Lili-Naz Hazrati from UHN’s Laboratory Medicine Program, Dr. Anne Bassett, who holds The Dalglish Family Chair in 22q11.2 Deletion Syndrome and Dr. Anthony Lang from the Krembil Neuroscience Centre, among others.

The researchers studied 159 adults with 22q11.2 deletion syndrome to examine how many had been clinically diagnosed with Parkinson’s disease.
Drs. Kiehl and Hazrati performed a post-mortem autopsy on  four individuals who had had the deletion and Parkinson’s disease in order to examine the brain tissue. 
With the deletion occurring in 2,000 to 4,000 births, it is often still under diagnosed; although patients with this condition may have been diagnosed with heart or other birth defects, learning or speech difficulties, and some may develop schizophrenia.
“Through a post-mortem examination, we were able to show that three patients had pathological changes that were typical of that seen in Parkinson’s disease.
Parkinson's symptoms unrelated to medications
The examination also helped to show that the symptoms of Parkinson’s disease were not related to side effects of the medications commonly used to treat schizophrenia,” said Kiehl, who co-authored the report with CAMH graduate student Nancy Butcher.
“Interestingly, the last patient had a loss of nerve cells in areas typically affected in Parkinson’s disease but lacked the classically intraneuronal inclusions called Lewy bodies – a protein that accumulates in the nerve cells in these types of disorders.
This is similar to another gene mutation (LRKK2- most common genetically acquired PD) leading to Parkinson’s disease.
"These findings will open a new window of opportunity to understand better the pathophysiology of Parkinson’s disease,” said co-author Hazrati.
Parkinson’s disease is one of the most common neurodegenerative disorders worldwide, most often occurring in people over the age of 65. Earlier onset of Parkinson’s disease, before age 50, is very rare and has never been associated with chromosome 22 in the past.
'Exciting' discovery
“Our discovery that the 22q11.2 deletion syndrome is associated with Parkinson’s disease is very exciting,” said Dr. Anthony Lang, Director of the Movement Disorders Program at the Krembil Neuroscience Centre of Toronto Western Hospital. “It is reminiscent of other genetic causes of Parkinson’s disease, and opens new directions to search for novel genes that could cause its more common form.”
“Studies of patients with 22q11.2 deletion syndrome before they even develop Parkinson’s disease may not only provide important information on the effectiveness of screening methods for early detection of the disease, but also allow for future ‘neuroprotective treatments’ to be introduced at the ultimate time when they can have a chance to make an important impact on preventing the disease or slowing its course,” Lang added.
During the autopsies, it was also noted that patients with the 22q11.2 deletion have abnormal accumulations of protein called Lewy bodies in the brain in some, but not all cases, just as in another genetic form of Parkinson’s disease.
“22q11.2 deletion syndrome has been fairly well studied in childhood and adolescence, but less is known about its effects as people age,” said Bassett, the Principal Investigator of the study and Director of CAMH's Clinical Genetics Research Program and Director of UHN's Dalglish Family Hearts and Minds Clinic in the Peter Munk Cardiac Centre. The Hearts and Minds Clinic is the world’s first clinic dedicated to adults with 22q11.2 deletion syndrome.
“Most people with 22q11.2 deletion syndrome will not develop Parkinson’s disease,” said Bassett. “But it does occur at a rate higher than in the general population. We will now be on the look-out for this so we can provide the best care for patients.”
The study suggests that patients with early-onset Parkinson’s disease, which have other symptoms associated with the 22q11.2 deletion, should be tested for this deletion on chromosome 22.
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