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Exonic rearrangements in DMD in Chinese Han individuals affected with Duchenne and Becker muscular dystrophies
Author(s) -
Ling Chao,
Dai Yi,
Fang Li,
Yao Fengxia,
Liu Zhe,
Qiu Zhengqing,
Cui Liying,
Xia Fan,
Zhao Chen,
Zhang Shuyang,
Wang Kai,
Zhang Xue
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23953
Subject(s) - breakpoint , duchenne muscular dystrophy , biology , genetics , exon , proband , gene , genome instability , gene duplication , exon skipping , mutation , dna , chromosomal translocation , alternative splicing , dna damage
Exonic deletions and duplications within DMD are the main pathogenic variants in Duchenne and Becker muscular dystrophies (DMD/BMD). However, few studies have profiled the flanking sequences of breakpoints and the potential mechanism underlying the breakpoints in different fragile regions of DMD . In this study, 896 Chinese male probands afflicted with DMD/BMD were selected from unrelated families and analyzed using multiplex ligation‐dependent probe amplification of the DMD gene, in which we identified exon deletions in 784 subjects and duplications in 112 subjects. Deletions occurred most frequently in the genomic region encompassing exons 45–55, accounting for 73% of all deletion patterns. Furthermore, to unravel the potential mechanism that induced breaks, DMD gene capture and sequencing were performed to identify the breakpoints in 37 subjects with deletions encompassing exons 45–55 of DMD ; we found that DMD instability did not arise from a single cause; instead, long‐sequence motifs, nonconsensus microhomologies, low‐copy repeats, and microindels were embedded around the breakpoints, which may predispose DMD to instability. In summary, this study highlights the heterogeneous characteristics of the flanking sequences around the breakpoints and helps us to understand the mechanism underlying DMD gene instability.