Gene Tied to Essential Tremor May Also Be Cause of Early Onset Parkinson’s

Mutations in the gene TNEM4, previously associated with essential tremor, may also be a cause of Parkinson’s disease, at least in its early onset form, a study reported.

However, this finding is only suggestive of a link and further research is necessary, its scientists said.

The study, “Rare variant analysis of essential tremor‐associated genes in early‐onset Parkinson’s disease,” was published in the Annals of Clinical and Translational Neurology.

Parkinson’s disease and essential tremor are movement disorders that can be similar in symptoms, including issues with tremor, bradykinesia — slowness or difficulty in body movement — and balance. These similarities suggest an overlap may exist in the biological processes that drive the disorders, but the processes themselves are not fully understood.

Researchers in China assessed whether mutations in 33 genes that have been previously associated with essential tremor might also associate with Parkinson’s. This analysis was done using genetic data from 1,494 people with early onset Parkinson’s disease (EOPD; disease onset at or before age 50) and 1,375 people without Parkinson’s, matched in terms of age and sex and serving as controls.

“To our knowledge, this is the first study to systematically analyze the association between rare variants of ET [essential tremor]‐associated genes in coding region and EOPD using a next‐generation sequencing method in a Chinese population,” the researchers wrote.

An initial statistical analysis indicated that mutations in TNEM4 — specifically, mutations that impair how this gene functions — were significantly associated with early onset Parkinson’s. TNEM4 was the only analyzed gene with such an association.

“Remarkably, only TENM4 gene had a suggestive association with EOPD, and none of the other rare damaging variants of ET‐associated genes were significantly associated with EOPD,” the researchers wrote.

Subsequent statistical analyses, which took into account factors like age and sex, indicated this finding of a link between TNEM4 and early onset Parkinson’s was “suggestive,” and not statistically significant. That is, mathematically, a probability exists that this finding was due to random chance.

The TNEM4 gene is expressed at high levels in the nervous system, and it is known to play roles in important neurological processes like regulating the production of myelin (the fatty substance that acts as a “sheath” around neurons, helping them to efficiently transmit electrical signals).

“Alterations to myelin have been described in [Parkinson’s disease] and [essential tremor] patients,” the researchers wrote, and as such, it could be feasible this gene may be involved in Parkinson’s.

“However,” they added, “the suggestive correlation of TENM4 and PD [Parkinson’s disease] still needs to be further replicated in additional cohorts.”

Further “genetic studies are required to replicate this result and may help to illuminate the potential genetic link between PD and ET,” the researchers added, noting they plan to also investigate “the potential genetic interplay between ET‐associated genes and late‐onset PD.”