Parkinson's breakthrough after gene mutation identified in Omani family

Discovery made after parents sought help when two daughters developed symptoms

Doctors at Sultan Qaboos University Hospital in Oman collaborated with a team at the VIB-KU Leuven Centre for Brain and Disease Research in Belgium. Photo: Sultan Qaboos University Hospital

Scientists have identified a genetic mutation associated with a form of early-onset Parkinsonism in an Omani family, revealing insights into how the disease develops.

The breakthrough was made after the family sought answers for why two daughters developed severe Parkinsonism – a group of disorders that share similar symptoms, including motor dysfunction and cognitive decline, at a young age. That led to the identification of a mutation in a gene known as SGIP1, which was not previously linked to the conditions.

Parkinson’s disease accounts for about 80 per cent of all cases of Parkinsonism. However, other conditions include multiple system atrophy or corticobasal degeneration. The most common forms usually develop after the age of 60, but some can develop earlier. Juvenile Parkinsonism begins on average at 17.

However, understanding how the mutation led to the development of the disease required further work. To do that, the women’s doctors at Sultan Qaboos University Hospital in Oman collaborated with a team at the VIB-KU Leuven Centre for Brain and Disease Research in Belgium.

They created a model using fruit flies which lacked the gene and developed symptoms similar to those seen in Parkinsonism. Closer examination revealed that the mutation caused defects in synapses, which allow brain cells to connect and communicate with each other.

Crucial structures in the synapses, which are responsible for recycling and breaking down proteins, were found to be missing – suggesting the [gene] mutation interferes with the brain’s ability to maintain healthy synapses, which may play a significant role in the development of Parkinsonism.

Prof Patrik Verstreken of VIB-KU told The National the discovery provides new insights into what drives the condition at a young age.

“It also adds to the growing understanding of how synaptic dysfunction contributes to neurodegenerative diseases more broadly and Parkinsonism in particular,” he said. “Such problems could explain the movement difficulties, the behavioural problems and brain cell degeneration.”

However, it is not clear whether the same process involving the gene mutation plays a role in the more common, late-onset form of Parkinson’s. More research is needed, said Prof Verstreken.

“This work reinforces the idea that maintaining synapse health is essential for neurone survival throughout life,” said Dr Marianna Decet, first author of the study. “Our findings highlight the importance of synaptic proteostasis – the balance and quality control of proteins in synapses – in protecting against neurological diseases like Parkinsonism.”

Sabine Kuenen, research partner and co-author of the study, said the discovery shows that even small changes in the genetic code can have “a profound impact” on brain function.

In June, a man living with Parkinson's in Scotland called a procedure to cure his tremors a “miracle” after becoming the first person in the UK to receive the treatment as part of a National Health Service clinical trial.

About 10 million people have Parkinson’s worldwide. It can be difficult to diagnose because there is currently no test, and symptoms – such as tremors, mild memory and thinking problems and sleep issues – vary and can often be mistaken for other illnesses.

However, scientists have recently also made breakthroughs in the detection of the disease, developing a blood test that uses artificial intelligence. It can predict a person’s risk of Parkinson’s seven years before the onset of symptoms by analysing eight blood-based biomarkers, whose concentrations are altered in patients with the condition. Another diagnostic test is being developed using a minimally invasive skin biopsy, which looks for an abnormal protein – phosphorylated alpha-synuclein (P-SYN) – associated with some degenerative brain disorders.