Abstract
Background: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the DMD gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of de novo variants could increase. Therefore, determining the differences between the carrier and de novo variants of the DMD gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future.Methods: A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers.Results: Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. De novo deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, de novo duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the DMD gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%).Conclusion: Compared to de novo deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present de novo.
Highlights
Duchenne muscular dystrophy (DMD) is an X-linked recessively inherited fatal muscle disease, with an incidence of 15.9–21.9 for every 100,000 live newborn males [1,2,3]
De novo deletions were more concentrated in hotspot regions than carrier deletions of DMD/Becker muscular dystrophy (BMD)
No clear bias was observed in the variant distribution between carriers, de novo duplications, and small mutations in DMD/BMD
Summary
Duchenne muscular dystrophy (DMD) is an X-linked recessively inherited fatal muscle disease, with an incidence of 15.9–21.9 for every 100,000 live newborn males [1,2,3]. It is characterized by progressive weakness and muscle atrophy, accompanied by pseudohypertrophy of the gastrocnemius and a positive Gowers sign. Patients usually die of cardiorespiratory failure in the second or third decade of life Pathogenic variants, such as deletions, duplications, and small mutations, in the DMD gene encoding dystrophin account for both DMD and Becker muscular dystrophy (BMD), a milder form of the disease with later onset and slower progression. Determining the differences between the carrier and de novo variants of the DMD gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
