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Objective: It remains unclear whether habitual physical activity can attenuate the rate of progressive muscle strength loss in individuals with myotonic dystrophy type 1 (DM 1). The aim of this study was to identify whether there were any strength differences between DM 1 patients who were habitually active or sedentary. Design: Knee extension, handgrip, and elbow flexion quantitative strength measurements were investigated in the DM 1 patients using isokinetic dynamometry. Strength was compared between the patients who followed self-selected formal exercise plans for at least 1 yr, those who were sedentary (controls), and those who initiated or terminated a formal exercise routine. Results: Physically active DM1 patients with midrange CTG repeat size (100 -500 CTG repeat sizes) had significantly stronger handgrip and knee extension and elbow flexion torques as compared with their sedentary counterparts with the same CTG repeat range. The DM 1 patients who began a formal exercise routine experienced a significant improvement in knee extension torque measurements (+24.3%) in comparison with those who were habitually active or sedentary. Conclusions: These data suggest that there is an association between physical activity and strength. This may be shown to be a useful tool for the management of this condition. Further investigations into the relationships between physical exercise, muscle weakness, and genetic factors are needed before evidence-based recommendations can be made. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases., Methods: We prospectively enrolled 297 probands who met eligibility criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests., Results: Laboratories reported 105 molecular diagnoses and 165 uncertain results in known and novel genes. Of these, clinicians interpreted 102 of 105 (97%) molecular diagnoses and 6 of 165 (4%) uncertain results as clinical-molecular diagnoses. The 108 clinical-molecular diagnoses were in 104 families (35% diagnostic yield). Each eligibility criteria resulted in diagnostic yields of 30% to 40%, and higher yields were achieved when >2 eligibility criteria were met (up to 45%). Hypothetical tests would have identified 61% of clinical-molecular diagnoses., Conclusion: We demonstrate robustness in eligibility criteria and high clinical validity of laboratory results from ES testing. The importance of ES was highlighted by the potential 40% of patients that would have gone undiagnosed without this test., Competing Interests: Conflict of Interest The authors declare no conflicts of interests., (Copyright © 2023. Published by Elsevier Inc.)

We examined the utility of clinical and research processes in the reanalysis of publicly-funded clinical exome sequencing data in Ontario, Canada. In partnership with eight sites, we recruited 287 families with suspected rare genetic diseases tested between 2014 and 2020. Data from seven laboratories was reanalyzed with the referring clinicians. Reanalysis of clinically relevant genes identified diagnoses in 4% (13/287); four were missed by clinical testing. Translational research methods, including analysis of novel candidate genes, identified candidates in 21% (61/287). Of these, 24 families have additional evidence through data sharing to support likely diagnoses (8% of cohort). This study indicates few diagnoses are missed by clinical laboratories, the incremental gain from reanalysis of clinically-relevant genes is modest, and the highest yield comes from validation of novel disease-gene associations. Future implementation of translational research methods, including continued reporting of compelling genes of uncertain significance by clinical laboratories, should be considered to maximize diagnoses., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)