Mutation in a New Gene Causing Parkinson Disease Identified


Muhammad Ali, the legendary boxer died on June 3, 2016 after a long battle of over three decades with the Parkinson’s disease (PD). After so many years of the identification of the PD, still there is no cure for the disease but recently, the researchers discovered a third important link to this neurodegenerative disorder.

Till now, the mutation in the two genes- SNCA and LRRK2 has been associated with the Parkinson’s, now the role of mutation in the third gene TMEM230 (transmembrane 230) has been brought forward by the researchers of Northwestern Medicine in the generation of Parkinson’s in a person. The protein encoded by TMEM230 is involved in encasing the neurotransmitter dopamine in neurons and Parkinson’s is characterized by the degradation of dopamine producing neurons.The study is published in Nature Genetics.

genes associated in parkinsons

Figure 1. Molecular pathways of Parkinson disease (Photo credit: Nat Rev Genet. 2006 Apr;7(4):306-18).

According to the recent findings, mutations in TMEM230 lead to “clinically typical, Lewy body–confirmed Parkinson’s disease”. TMEM230 encodes a protein that goes to secretory or recycling vesicles including synaptic vesicles present in neurons. The synaptic vesicles transmembrane proteins function by uptaking neurotransmitters in synaptic vesicles for circulation among cells and trafficking the proteins which regulate the intracellular traffic of synaptic vesicles. TMEM230 mutation disturbs this “synaptic vesicle trafficking”.

synaptic vessels

Figure 2. The synaptic vesicle cycle (Photo credit:

We believe that vesicle trafficking defects are a key mechanism of Parkinson’s disease, not just for cases with this mutation, but a common pathway for the majority of cases. All three of the authenticated genes are concentrated on synaptic vesicles,” Deng, first author of the study said. “Our new findings suggest that normalizing synaptic vesicle trafficking may be a strategy for future therapeutic development. We can develop drugs to promote this critical pathway“.

Genome- wide analysis was done on 65 members of a family including 13 members having PD to identify a common mutation responsible for the disease. Finally, they narrowed their search to a particular region of DNA on chromosome 20 which contained 141 known genes.They compared the DNA variations and genetic differences using whole exome sequencing technology. Ultimately they identified TMEM230 as the gene whose mutation causes PD.   

TMEM230 mutation was also explored and found in the PD patients of North America and Asia who showed clinical characteristics of the disease as well as pathological evidences was also observed in the brain.

It’s worldwide, found in very different ethnic and environmental conditions. These mutations are that strong.” said principal investigator Dr. Teepu Siddique, the Les Turner ALS Foundation/Herbert C. Wenske Foundation Professor at Northwestern University Feinberg School of Medicine.

PD is a progressive neurodegenerative disorder clinically characterized by movement related disorders like shaking, stiffness, slow movement, difficulty in walking later leading to the advanced problems like dementia and behavioral disorders. It is the second most common neurodegenerative disease after Alzheimer’s Disease. According to a report, in 2013, 53 million people were affected by PD and about 103,000 died globally. More than 1 million cases of PD arise in India every year.

Scientists have been continuously involved in the development of a cure for the disease. The disease is being heavily funded every year. In 2016, National Institute of Health (NIH) funded around $152 million for the disease.

The recent breakthrough finding regarding the TMEM230 may provide an insight into the crumbling of the neurons inside the brain and help to build the foundation of the future treatment of the disease.

Featured image credit: Digital illustration of chromosome in colour background © krishnacreations (Stock Photo ID: 83315477)

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