Scoring Algorithm‐Based Genomic Testing in Dystonia: A Prospective Validation Study

Abstract

Despite the limitations, including a short follow-up period and small sample size, this pilot study suggests that FUS Vo-thalamotomy may be an alternative treatment option for patients with FHD. A randomized controlled study with a larger sample size and a longer follow-up period is warranted to elucidate the efficacy and safety of MRgFUS Vo-thalamotomy for FHD.Acknowledgments: We thank Kaoru Shimizu from the Intelligent Clinical Research and Innovation Center at the Tokyo Women's Medical University for her invaluable assistance in the conduct of this study.

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia

“…For detailed clinical characteristics and a review of previously reported cases, see Table 1 and Supplementary Table 3. Genotype information from families 1 and 2 has been published previously [11,12].…”

“…Genetic studies in families 1 and 2 have been described [11,12]. WES on genomic DNA isolated from the blood lymphocytes of the subjects in families 3 and 4 was carried out using previously reported methods [13].…”

“…Sequence-data analysis and interpretation were performed at the Helmholtz Center Munich and Technical University of Munich (Munich, Germany) using a validated in-house-developed bioinformatics pipeline, as described [14]. In family 1, the exomes of two affected siblings and the unaffected father had been sequenced [11,12]; in family 2, quartet WES (two affected siblings plus unaffected parents) had been performed [11]; in family 3, we performed trio WES (index patient plus unaffected parents); and in family 4, only the index patient underwent WES. The affected individuals' entire WES data sets were searched for pathogenic or likely pathogenic variants in reported disorder-associated genes, as detailed earlier [13,15].…”

A novel diagnostic approach for patients with adult-onset dystonia

“…To our knowledge, our diagnostic approach is the first algorithm that covers all forms of adult-onset dystonia, including acquired, neurodegenerative and genetic causes. The recommendation to refrain from further investigations in patients with AOIFD at step 5 of our algorithm, is in line with a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of genetic testing by using WES 49. According to this prediction tool, which was based on a large exome-wide study,50 an AOIFD-phenotype will lead to a sum score of 0 or 1 points, indicating that genetic testing is not recommended.…”

“…According to this prediction tool, which was based on a large exome-wide study,50 an AOIFD-phenotype will lead to a sum score of 0 or 1 points, indicating that genetic testing is not recommended. Both in the prediction tool49 as in our algorithm the clinical characteristics ‘age at onset’, ‘body distribution’ and ‘associated features’ are incorporated. However, in the criteria of the prediction tool ‘temporal pattern’ is not included and no distinction is made between typical (Table 1) and atypical dystonias, such as focal leg dystonia which can be an important clue for an underlying inherited condition, or lead to a diagnosis of an acquired or neurodegenerative disorder earlier in the diagnostic process.…”