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Genotype–phenotype correlation in Becker muscular dystrophy in Chinese patients

Abstract

Large deletions and duplications are the most frequent causative mutations in Becker muscular dystrophy (BMD), but genetic profile varied greatly among reports. We performed a comprehensive molecular investigation in 95 Chinese BMD patients. All patients were divided into three subtypes: normal muscle strength (type 1) in 18 cases, quadriceps myopathy (type 2) in 20 cases, and limb-girdle weakness (type 3) in 57 cases. Nineteen cases (20.0%) had small mutations and 76 cases (80.0%) had major rearrangements, including 67 cases (70.5%) of exonic deletions and 9 cases (9.5%) of exonic duplications. We identified 50 cases (65.8%) of in-frame mutations, and 26 cases (34.2%) of frame-shift mutations. The frequency of deletion in exons 13–19 was 30.6% in type 1 patients, 9.7% in type 2 patients, and 10.4% in type 3 patients. The frequency of deletion in exons 45–55 was 28.6% in type 1 patients, 40.8% in type 2, and 50.0% in type 3 patients. All major rearrangements of DMD gene in type 1 patients were also observed in type 3 patients. Our study suggested that frame-shift mutation was not rare in Chinese BMD patients. Although no difference was observed on the forms of DMD gene mutations among the three types of patients, the mutation in proximal region of DMD gene has higher frequency for patients without weakness. Effect of exon skipping for DMD depends on the size and location of the mutation. Additional studies are required to determine whether exon-skipping strategies in proximal region of DMD gene could yield more functional dystrophin.

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Acknowledgements

We thank all patients and their family members for their participation in this study. We also thank Ms Jing Liu and Ms Yuehuan Zuo for their technical assistance in the preparation of genetic analysis.

Funding

This study was supported by the Ministry of Science and Technology of China (No. 2011ZX09307-001-07) and Beijing Municipal Science and Technology Commission (No. Z151100003915126).

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Correspondence to Yun Yuan.

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The work described here has not been published previously, nor is it under consideration for publication elsewhere. This publication has been approved by all the authors and by the responsible authority where the work was carried out. If this paper is accepted, it will not be published elsewhere in the same form or in any other language, without the written consent of the copyright-holder. The authors declare that they have no conflict of interest.

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Yuan, R., Yi, J., Xie, Z. et al. Genotype–phenotype correlation in Becker muscular dystrophy in Chinese patients. J Hum Genet 63, 1041–1048 (2018). https://doi.org/10.1038/s10038-018-0480-5

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