Objective: To verify the role of COL6A3 in isolated dystonia.

Background: COL6A3 has recently been suggested to cause a form of autosomal recessive isolated dystonia. Until now, there is limited information about Col6A3 gene test in Asian population. Herein, we performed comprehensive COL6A3 mutation screenings in 179 sporadic isolated dystonia patients from Chinese population, including 57 early-onset cases.

Methods: We collected blood samples and used Polymerase chain reactions (PCR) to amplify 43 coding exons and intron 41 of COL6A3 (NM_004369.3). Mutational screening was performed by direct sequencing. All patients were negative for the genetic testing of TOR1A, THAP1, CIZ1, GNAL and ANO3.

Results: None of the reported disease-causing mutations were found. As a result, we identified one patient with compound heterozygotes of maternal and paternal origin (c.5000A>G[p.D1667G] and c.7570C>T[p.P2524S](Fig 1). Bioinformatics analysis demonstrated that both variants exhibit highly conserved residues across species. Structural analysis revealed hydrogen bonding interaction disruption in D1667G and free energy increase in P2524S. Besides, 8 other variants were found in 8 dystonia patients separately.

Conclusions: Our study revealed that mutation in COL6A3 is not a major cause of sporadic isolated dystonia, at least in Chinese population. Functional analysis D1667G and P2524S and validation in a larger study from a more diverse ethnic population are needed to ascertain the role of COL6A3.

References: [1] Zech M, Lam DD, Francescatto L, et al. Recessive mutations in the α3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia. Am J Hum Genet. 2015. 96(6): 883-93. [2] Lohmann K, Schlicht F, Svetel M, et al. The role of mutations in COL6A3 in isolated dystonia. J Neurol. 2016. 263(4): 730-4. [3] Bönnemann CG. The collagen VI-related myopathies: muscle meets its matrix. Nat Rev Neurol. 2011. 7(7): 379-90.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/screening-study-of-col6a3-in-sporadic-isolated-dystonia/