Lessons learned from the first national population-based genetic carrier-screening program for Duchenne muscular dystrophy

Purpose: To summarize the results of first year implementation of pan-ethnic screening testing for Duchenne muscular dystrophy (DMD) and present the ensuing challenges. Methods: Data acquisition for this study was performed by retrospective search of Ministry of Health registry for reports of all laboratories performing genetic screening tests. DMD testing was performed by multiplex ligation-dependent probe amplification technology. In case of single-exon deletion, sequencing of the specific exon was performed to rule out underlying single-nucleotide variant. Results: Of overall 85,737 DMD tests, 82 clinically significant findings were noted (0.095%, or 1:1,046 women). In addition, 80 findings with uncertain clinical significance were detected (0.093%, or 1:1072), as well as 373 cases (0.4%, or 1:230) of single-exon deletions subsequently identified as false positives because of underlying single-nucleotide variant, mostly variants in exon 8 in North African Jewish population, and in exon 48 in Arab Muslim population. Conclusion: Interpretation of population-based DMD carrier screening is complex, occasionally requiring additional genetic testing methods and ethical considerations. Multicenter data registry, including ethnic origin and familial segregation in selected cases, is crucial for optimal definition of the results during genetic counseling and informed decisions regarding prenatal testing. (c) 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Automated summary

The study summarizes the results of the first year of implementation of pan-ethnic screening testing for Duchenne muscular dystrophy (DMD) and discusses the challenges that follow. The study found clinically significant results in 82 cases, uncertain clinical significance in 80 cases, and false positive results in 373 cases initially identified as single-exon deletions. Interpreting population-based DMD carrier screening requires additional genetic testing methods and ethical considerations.