Objective: In this context, it is important to reveal the mutation frequency of primary dystonia related genes using target dystonia related gene panel among a relatively large cohort of Chinese patients with EODYT, as well as study the genotype-phenotype correlations.

Background: Although DYT1 gene mutation is the most common genetic cause for primary early onset generalized dystonia (EODYT), several other genes such as GCH1, TH, CSE, PRRT2, MR1, SGCE, and ATP1A3 have also been reported to be genetic cause for EODYT. However, mutation frequency and genotype-phenotype correlation remain largely unknown in Chinese patients with early-onset primary dystonia (EODYT).

Method: A total of 150 Chinese patients with EODYT underwent dystonia related gene targeted panel sequencing, and we only included the definite DYT monogenic causative genes into the analysis. Sanger sequencing was performed for the selected variants.

Results: Totally, 40 patients (26.7%) were found to have likely genetic causes for dystonia, those include 30 patients (20%) carrying pathogenic or likely pathogenic variants, and the other 10(6.7%) patients carrying VUS. Among the different subtypes, myoclonus dystonia(42.9%) had the highest proportion for likely genetic causes, followed by and generalized dystonia (34.7%) and paroxysmal dystonia(33.3%). Among different genes, the highest mutation frequency was found in TOR1A (10/150, 6.7%), followed by SGCE (8/150, 5.3%) and GCH1 (5/150, 3.3%).

Conclusion: The first and largest targeted panel sequencing study on a large cohort of Chinese patients with EODYT provided a comprehensive genetic landscape for EODYT. Moreover, our findings of unusual phenotypes and novel variants also expanded the phenotype and genetic spectrum for patients with EODYT.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mutation-screening-and-clinical-features-analysis-in-patients-with-early-onset-primary-dystonia/