Genetic Screening of a Hungarian Cohort with Focal Dystonia Identified Several Novel Putative Pathogenic Gene Variants

András Salamon; Zsófia Flóra Nagy; Margit Pál; Máté Szabó; Ádám Csősz; László Szpisjak; Gabriella Gárdián; Dénes Zádori; Márta Széll; Péter Klivényi

doi:10.3390/ijms241310745

Genetic Screening of a Hungarian Cohort with Focal Dystonia Identified Several Novel Putative Pathogenic Gene Variants

Int J Mol Sci. 2023 Jun 28;24(13):10745. doi: 10.3390/ijms241310745.

Authors

Affiliations

¹ Department of Neurology, University of Szeged, 6, Semmelweis Str., H-6725 Szeged, Hungary.
² Department of Medical Genetics, University of Szeged, 4, Somogyi Béla Str., H-6720 Szeged, Hungary.
³ Institute of Genomic Medicine and Rare Disorders, Semmelweis University, 78/b, Üllői Str., H-1083 Budapest, Hungary.
⁴ ELKH-SZTE Functional Clinical Genetics Research Group, Eötvös Loránd Research Network, 4, Somogyi Béla Str., H-6720 Szeged, Hungary.

Abstract

Dystonia is a rare movement disorder which is characterized by sustained or intermittent muscle contractions causing abnormal and often repetitive movements, postures, or both. The two most common forms of adult-onset focal dystonia are cervical dystonia (CD) and benign essential blepharospasm (BSP). A total of 121 patients (CD, 74; BSP, 47) were included in the study. The average age of the patients was 64 years. For the next-generation sequencing (NGS) approach, 30 genes were selected on the basis of a thorough search of the scientific literature. Assessment of 30 CD- and BSP-associated genes from 121 patients revealed a total of 209 different heterozygous variants in 24 genes. Established clinical and genetic validity was determined for nine heterozygous variations (three likely pathogenic and six variants of uncertain significance). Detailed genetic examination is an important part of the work-up for focal dystonia forms. To our knowledge, our investigation is the first such study to be carried out in the Middle-European region.

Keywords: blepharospasm; cervical dystonia; dystonia; focal; genetic.

MeSH terms

Adult
Blepharospasm* / diagnosis
Dystonic Disorders* / diagnosis
Dystonic Disorders* / genetics
Genetic Testing
Humans
Hungary
Middle Aged
Torticollis* / diagnosis
Torticollis* / genetics

Grants and funding

This work was supported by the Hungarian Brain Research Program 2.0 (Grant No. 2017-1-1.1.2.1-NKP-2017-0002) and Drug Research and Development Program (TKP-2021-EGA-32). This research work was conducted with the support of the Szeged Scientists Academy under the sponsorship of the Hungarian Ministry of Innovation and Technology FEIF/646-4/2021-ITM_SZERZ. András Salamon received funding from the National Scholarship for Young Talents–NTP-NFTÖ-21-B-0100.