The importance of genetic testing for dystonia patients and translational research

Abstract

Genetic testing through a variety of methods is a fundamental but underutilized approach for establishing the precise genetic diagnosis in patients with heritable forms of dystonia. Our knowledge of numerous dystonia-related genes, variants that they may contain, associated clinical presentations, and molecular disease mechanism may have significant translational potential for patients with genetically confirmed dystonia or their family members. Importantly, genetic testing permits the assembly of patient cohorts pertinent for dystonia-related research and developing therapeutics. Here we review the genetic testing approaches relevant to dystonia patients, and summarize and illustrate the multifold benefits of establishing an accurate molecular diagnosis for patients imminently or for translational research in the long run.

Dystonia and deep brain stimulation: correlation between genetic mutation and clinical outcome

“…Diagnostics includes neuroimaging (MRI) and genetic testing (7). e method or technology chosen for genetic testing should be determined based on the clinical presentation at onset and the most recent examination, family history, availability of the particular diagnostic test, experience of the physician and other factors (8). Despite the aforementioned, the diagnosis relies mainly on clinical evaluation.…”

“…Carrier and predictive testing are similar. ey are used for individuals suspected of carrying a pathogenic variant, these people are una ected, but have a family history of dystonia (8). Finally, prenatal genetic testing is used to determine whether a fetus has a presumed disease-causing change before birth (8).…”

“…ey are used for individuals suspected of carrying a pathogenic variant, these people are una ected, but have a family history of dystonia (8). Finally, prenatal genetic testing is used to determine whether a fetus has a presumed disease-causing change before birth (8). e types of genetic tests available for dystonia include simple single-variant testing and single-gene Sanger sequencing to advanced nextgeneration sequencing (NGS) based approaches such as NGS gene panels, clinical exome sequencing (CES), whole-exome sequencing (WES) or whole-genome sequencing (WGS) (8).…”

“…Copy number variation (CNV) analysis may be required in some cases. Which approach or technology will be used should be determined individually, as it depends on the clinical presentation at the time of onset and at the most recent examination, family history, availability of the speci c diagnostic test and the physician's experience (8). Di erent hereditary forms of dystonia are caused by defects in various genes, which leads to various pathophysiological pathways.…”

Untwisting dystonia: stepping-up genetics, shifting pathophysiology, and strategizing care

“…The introductory article updates on the definition and nomenclature of dystonia as well as on the two classification axes (clinical and etiological) (Grütz and Klein 2021). The following contributions focus on genetic aspects of dystonia by reviewing the present knowledge of hereditary isolated (Domingo et al 2020), combined (Weissbach et al 2020), complex (Herzog et al 2020), and paroxysmal disease forms (Liao et al 2021), and the relevance of genetic testing (Pozojevic et al 2021). Importantly, through the expedite uncovering of the genetic basis of monogenic dystonias, new molecular mechanisms underlying the disease process have emerged and indicated several areas of functional convergence among the relevant proteins (Gonzalez-Latapi et al 2021).…”