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On-line Access: 2019-08-05

Received: 2018-10-28

Revision Accepted: 2019-03-25

Crosschecked: 2019-07-09

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Citations:  Bibtex RefMan EndNote GB/T7714


Yan-mei Yang


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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.9 P.753-765


Comprehensive genetic diagnosis of patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and pathogenicity analysis of splice site variants in the DMD gene

Author(s):  Yan-mei Yang, Kai Yan, Bei Liu, Min Chen, Li-ya Wang, Ying-zhi Huang, Ye-qing Qian, Yi-xi Sun, Hong-ge Li, Min-yue Dong

Affiliation(s):  Department of Reproductive Genetics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China; more

Corresponding email(s):   dongmy@zju.edu.cn

Key Words:  Dystrophin gene, Variation, Genetic diagnosis, Splice site mutation, Hybrid minigene splicing assay

Yan-mei Yang, Kai Yan, Bei Liu, Min Chen, Li-ya Wang, Ying-zhi Huang, Ye-qing Qian, Yi-xi Sun, Hong-ge Li, Min-yue Dong. Comprehensive genetic diagnosis of patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and pathogenicity analysis of splice site variants in the DMD gene[J]. Journal of Zhejiang University Science B, 2019, 20(9): 753-765.

@article{title="Comprehensive genetic diagnosis of patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and pathogenicity analysis of splice site variants in the DMD gene",
author="Yan-mei Yang, Kai Yan, Bei Liu, Min Chen, Li-ya Wang, Ying-zhi Huang, Ye-qing Qian, Yi-xi Sun, Hong-ge Li, Min-yue Dong",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Comprehensive genetic diagnosis of patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and pathogenicity analysis of splice site variants in the DMD gene
%A Yan-mei Yang
%A Kai Yan
%A Bei Liu
%A Min Chen
%A Li-ya Wang
%A Ying-zhi Huang
%A Ye-qing Qian
%A Yi-xi Sun
%A Hong-ge Li
%A Min-yue Dong
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 9
%P 753-765
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800541

T1 - Comprehensive genetic diagnosis of patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and pathogenicity analysis of splice site variants in the DMD gene
A1 - Yan-mei Yang
A1 - Kai Yan
A1 - Bei Liu
A1 - Min Chen
A1 - Li-ya Wang
A1 - Ying-zhi Huang
A1 - Ye-qing Qian
A1 - Yi-xi Sun
A1 - Hong-ge Li
A1 - Min-yue Dong
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 9
SP - 753
EP - 765
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800541

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the DMD gene. The aim of this study is to identify pathogenic DMD variants in probands and reduce the risk of recurrence of the disease in affected families. variations in 100 unrelated DMD/BMD patients were detected by multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS). Pathogenic variants in DMD were successfully identified in all cases, and 11 of them were novel. The most common mutations were intragenic deletions (69%), with two hotspots located in the 5' end (exons 2–19) and the central of the DMD gene (exons 45–55), while point mutations were observed in 22% patients. Further, c.1149+1G>A and c.1150−2A>G were confirmed by hybrid minigene splicing assay (HMSA). This two splice site mutations would lead to two aberrant DMD isoforms which give rise to severely truncated protein. Therefore, the clinical use of MLPA, NGS, and HMSA is an effective strategy to identify variants. Importantly, eight embryos were terminated pregnancies according to prenatal diagnosis and a healthy boy was successfully delivered by preimplantation genetic diagnosis (PGD). Early and accurate genetic diagnosis is essential for prenatal diagnosis/PGD to reduce the risk of recurrence of DMD in affected families.



关键词: DMD基因;突变;遗传学诊断;剪接突变;Minigene剪接实验

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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[42]List of electronic supplementary materials

[43]Table S1 Oligonucleotide primers for detection of mutations in DMD gene

[44]Table S2 Deletions in DMD gene detected by MLPA

[45]Table S3 Duplications in DMD gene detected by MLPA

[46]Table S4 Point mutations in DMD gene detected by NGS

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