Objective: The aim of our study was to establish prevalence of variants in the gene for anoctamin 3 (ANO3) in a population of patients with cervical dystonia.

Background: Cervical dystonia is a hyperkinetic movement disorder characterized by contractions of cervical musculature that lead to abnormal movements or abnormal posture of the head. Combination of both genetic and epigenetic factors plays role in development of the disease. List of genes associated with dystonia is constantly expanding, although prevalence of gene variants and diversity of phenotypic spectrum is not yet well understood. Our study was focused on the incidence of variants in one of these genes – ANO3, located on chromosome 11, consisting of 27 exons, and with particularly high expression in the striatum.

Methods: After obtaining informed consent, 32 consecutive patients (5 men, 27 women, mean age 59.0 ± 14.7 years) from a specialized neurological clinic focusing on the treatment of dystonia were enrolled. The average age at onset of dystonia was 43.1 ± 15.0 years (min. 13, max 66 years). DNA was analysed using direct Sanger sequencing. All 27 exons with adjacent intron and 5′-UTR and 3′-UTR regions were screened. Significance of the observed variations was predicted by the MutationTaster® software.

Results: We did not reveal any of the 13 missense mutations located in exons referred up to date in our sample. However, few very rare (frequency of minor allele <0.01) or yet undescribed variants in intron regions were detected. One of these intron’s variants (NM_031418.3:c.693-10_693-9insT; rs753255476) was located in the splicing area at the border of exon and intron, and has been evaluated by predicting software as a potential disease-causing variation. Rare variants found in the 3′-UTR region are located in the hypersensitive region of DNase I that affects transcriptional activity.

Conclusions: According to our preliminary findings, not only rare exon variants, but also variants in introns and UTR regions of the ANO3 gene might contribute to the ethiopathogenesis of dystonia. Further extensive studies and functional analyses are needed to verify these findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/variations-in-ano3-gene-in-patients-with-cervical-dystonia/