Parkinson Disease and Essential Tremor Gene Found

01 December 2014 Comments Off on Parkinson Disease and Essential Tremor Gene Found

Bilkent University researchers have played a leading role in the identification of a gene that causes Parkinson disease and essential tremor, conditions that afflict many millions of people worldwide. The scientists who conducted the investigation said their study is the first clue that links two common movement disorders and could lead to new treatments.

Under the title “Mitochondrial Serine Protease HTRA2 p.G399S in a Kindred with Essential Tremor and Parkinson Disease,” the study was published the week of November 24 in the Early Edition of the Proceedings of the National Academy of Sciences (USA).

The investigation was a collaborative effort, involving researchers at both Bilkent and the University of Washington, along with clinicians at Hacettepe and Ankara Universities. The team studied a remarkable kin group from Central Anatolia: a six-generation consanguineous Turkish family with both essential tremor and Parkinson disease.

Essential tremor is the most frequent movement disorder of humans and can be associated with substantial disability. The worldwide prevalence is 0.9%, increasing to more than 4% in elderly populations.

Parkinson disease is the second most common neurodegenerative disorder, with a prevalence of 0.3% among the entire population in industrialized countries. The prevalence may rise as high as 1% in those over 60 years of age, and 4% in those over 80. It is estimated that Parkinson disease affects 7 million people globally.

Clinicians have for decades been perplexed by the observation that some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. The Turkish kin group offered scientists a key to elucidating the connection.

After carrying out whole exome sequencing and pedigree analysis in the family, the researchers identified mitochondrial serine protease HTRA2 as the gene likely to be responsible for both conditions. The same mutation had previously been associated with Parkinson characteristics in mouse mutants.

In the Turkish family, inheriting the mutation from one parent (heterozygous) or both parents (homozygous) resulted in essential tremor. However, homozygosity was associated with earlier age, with the onset of tremor occurring in the teens or twenties, and more severe tremor.

Homozygotes, but not heterozygotes, developed Parkinson signs in middle age. The disease is caused by the loss of nerve cells in the brain that produce the chemical dopamine, which helps to control mood and movement.

“We are now studying many more families with essential tremor and Parkinson disease,” said one of the principal authors of the study, Dr. Ayşe Tekinay of the Institute of Materials Science and Nanotechnology at Bilkent.

Geneticists have known for many years that consanguinity, along with multiple children, facilitates gene identification studies that target rare diseases. But it was not explicitly clear until recently that this could also be true for complex and common disease entities such as neurodegeneration, obesity or diabetes.

“I am confident that we will find more genes implicated in complex common diseases through the study of large consanguineous families,” added Prof. Tayfun Özçelik, dean of the Faculty of Science at Bilkent and a member of the Turkish Academy of Sciences.

At present, there is no cure for either essential tremor or Parkinson disease, but medication and brain stimulation can alleviate symptoms in both conditions.

Prof. Mary-Claire King, noted human geneticist, Lasker awardee and a member of the University of Washington Genome Sciences Center, said, “We are very excited about the results of Prof. Tekinay’s research. This is the way forward to understanding the molecular bases of movement disorders and developing new treatment strategies.”