Linkage of familial essential tremor to chromosome 5q35

Hicks, James E.; Konidari, Ioanna; Scott, Burton L.; Stajich, Jeffrey M.; Ashley-Koch, Allison E.; Gilbert, John R.; Scott, William K.

doi:10.1002/mds.26582

Cited by 15 publications

(9 citation statements)

References 30 publications

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“…A genetic linkage analysis identified four loci within which genes related to ET could be located. These areas are sited on chromosome 3q13 (ETM1) [ 21 ], 2p25–p22 (ETM2) [ 22 ], 6p23 (ETM3) [ 23 ], and 5q35 (no specific name) [ 24 ]. In the ETM1 region (3q13.3), the gene that encodes the dopamine receptor D3 ( DRD3 ) can be found.…”

Section: Essential Tremor (Et)mentioning

confidence: 99%

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Kosmowska

Wardas

2021

Biomolecules

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Essential tremor (ET) is one of the most common neurological disorders that often affects people in the prime of their lives, leading to a significant reduction in their quality of life, gradually making them unable to independently perform the simplest activities. Here we show that current ET pharmacotherapy often does not sufficiently alleviate disease symptoms and is completely ineffective in more than 30% of patients. At present, deep brain stimulation of the motor thalamus is the most effective ET treatment. However, like any brain surgery, it can cause many undesirable side effects; thus, it is only performed in patients with an advanced disease who are not responsive to drugs. Therefore, it seems extremely important to look for new strategies for treating ET. The purpose of this review is to summarize the current knowledge on the pathomechanism of ET based on studies in animal models of the disease, as well as to present and discuss the results of research available to date on various substances affecting dopamine (mainly D3) or adenosine A1 receptors, which, due to their ability to modulate harmaline-induced tremor, may provide the basis for the development of new potential therapies for ET in the future.

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Section: Essential Tremor (Et)mentioning

confidence: 99%

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Kosmowska

Wardas

2021

Biomolecules

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“…Altogether 33 loci and genes were selected as ET‐associated from genetic studies and were analyzed in our study (Table 1). Despite the ETM3 locus on chromosome 6p23 and a locus on chromosome 5 having been previously linked to ET in previous studies, no pathogenic variants were identified in these candidate regions and were not included in our analysis 22,23 . In our study, a total of 1494 EOPD patients (AAO ≤ 50) including sporadic EOPD and EOPD probands with a positive family history of PD and 1375 age and sex‐matched controls were collected to perform WES.…”

Section: Resultsmentioning

confidence: 99%

Rare variant analysis of essential tremor‐associated genes in early‐onset Parkinson’s disease

Liang

Zhao

Pan

et al. 2020

Ann Clin Transl Neurol

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Objective Parkinson’s disease (PD) and essential tremor (ET) are the two most common movement disorders. A significant overlap in clinical features, epidemiology, imaging, and pathology suggests that PD and ET may also share common genetic risk factors. Previous studies have only assessed a limited number of ET‐associated genes in PD patients and vice versa. Consequently, the genetic association between PD and ET remains incompletely characterized. In this study, we systematically investigated a potential association between rare coding variants in ET‐associated genes and PD, in a relatively large Chinese population cohort. Methods To investigate the genetic association between ET and PD, we performed the sequence kernel association testing (SKAT‐O) to explore the variant burden of 33 ET‐associated genes, using whole‐exome sequencing (WES) data from 1494 early‐onset PD (EOPD) patients and 1357 control subjects from mainland China. Results We report that rare loss‐of‐function and damaging missense variants of TNEM4 are suggestively associated with EOPD (P = 0.026), damaging missense variants of TNEM4 alone are also suggestively associated with EOPD (P = 0.032). No other rare damaging variants in ET‐related genes were significantly associated with EOPD. Interpretation This is the first systematic analysis of ET‐associated genes in EOPD. The suggestive association between TNEM4 and EOPD provides new evidence for a genetic link between ET and PD.

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“…The present study suggests that the selective antagonists for D 3 receptors or agonists for D 1/5 receptors may have a therapeutic potential. Interestingly, linkage analysis of genes associated with essential tremor identified four loci: chromosome 3q13 ( ETM1 ) ( Gulcher et al, 1997 ), 2p22-p25 ( ETM2 ) ( Higgins et al, 1997 ), 6p23 ( ETM3 ) ( Shatunov et al, 2006 ), and 5q35 ( Hicks et al, 2016 ), among which ETM1 contains the DRD3 gene encoding D 3 receptors ( Gulcher et al, 1997 ). In addition, DRD3-Gly (Ser9Gly variant), which shows a greater affinity for dopamine than the non-mutated form, is reportedly associated with the risk of essential tremor ( Jeanneteau et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Underlying Dopaminergic Regulation of Nicotine-Induced Kinetic Tremor

Kato

Kunisawa²,

Shimizu³

et al. 2022

Front. Pharmacol.

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Nicotine induces kinetic tremor, which resembles pharmacological features of essential tremors, via activating the inferior olive (IO) neurons. Since nicotine is known to enhance dopamine release by stimulating α4β2 and/or α6 nACh receptors, we examined the effects of various dopamine receptor ligands on nicotine-induced tremor to clarify the role of the dopaminergic system in modulating nicotine tremor. A tremorgenic dose of nicotine increased the dopamine level in the pons and medulla oblongata (P/MO), and the levels of dopamine metabolites in the hippocampus, P/MO, and striatum. Treatment of animals with the D1/5 agonist SKF-38393 inhibited the induction of nicotine tremor, whereas the D3 agonist PD-128,907 facilitated nicotine-induced tremor. The D2 agonist sumanirole showed no effect. In addition, nicotine tremor was significantly enhanced by the D1/5 antagonist SCH-23390 and inhibited by the D3 antagonist U-99194. Neither the D2 (L-741,626) nor D4 (L-745,870) antagonist affected the generation of nicotine tremor. Furthermore, microinjection of U-99194 into the cerebellum significantly inhibited nicotine-induced tremor, whereas its injection into IO or the striatum did not affect tremor generation. Although intrastriatal injection of SCH-23390 showed no effects, its injection into IO tended to enhance nicotine-induced tremor. The present study suggests that dopamine D3 and D1/5 receptors regulate the induction of nicotine tremor in an opposite way, D3 receptors facilitately and D1/5 receptors inhibitorily. In addition, the cerebellar D3 receptors may play an important role in modulating the induction of nicotine tremor mediated by the olivo-cerebellar system.

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Linkage of familial essential tremor to chromosome 5q35

Abstract: A locus on chromosome 5 is linked to essential tremor. Further research is needed to identify a causative variant. © 2016 International Parkinson and Movement Disorder Society.

Cited by 15 publications

References 30 publications

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Rare variant analysis of essential tremor‐associated genes in early‐onset Parkinson’s disease

Mechanisms Underlying Dopaminergic Regulation of Nicotine-Induced Kinetic Tremor

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