Identification of two rare mutations c.1318G>A and c.6438+2T>G in a Chinese DMD family as genetic markers
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Online ISSN 2092-9293 Print ISSN 1976-9571
RESEARCH ARTICLE
Identification of two rare mutations c.1318G>A and c.6438+2T>G in a Chinese DMD family as genetic markers Yingchuan Zhu1 · Lijun Yang1 · Tengjiao Ma1 · Yilu Lu1 · Dachang Tao1 · Yunqiang Liu1 · Yongxin Ma1 Received: 3 March 2020 / Accepted: 15 July 2020 © The Genetics Society of Korea 2020
Abstract Background Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder with no effective treatment, which underscores the importance of avoiding the birth of children with DMD by identifying pathogenic mutations and obtaining an accurate prenatal diagnosis. Objective The objective of this study was to analyze the genetic defect of a Chinese family where all male patients have died of DMD. Methods Multiplex ligation dependent probe analysis (MLPA) and next-generation sequencing (NGS) were employed to detect DMD mutations. The candidate mutations were then validated by Sanger sequencing. In vitro splicing assay was further conducted to examine the potential effect of the novel DMD splice site mutation on splicing. Results We found that two rare DMD mutations c.1318G>A and c.6438+2T>G passed from generation to generation among female carriers and they may be used as genetic markers in the Chinese DMD family. In vitro splicing assay further revealed that the novel classical splice site mutation c.6438+2T>G gave rise to a new donor splice site, which resulted in a frame shift of the transcripts and a premature termination at position 2159 in exon 45 (p.Y2144Nfs*16). Conclusion We found that two co-inherited mutations passed from generation to generation in female carriers and they may be used as genetic markers in the Chinese DMD family. Our findings not only expanded the DMD mutation spectrum, but also provided an important basis for identifying of female carriers and avoiding the birth of affected male children in this DMD family. Keywords Duchenne muscular dystrophy (DMD) · DMD · Next-generation sequencing (NGS) · Splice site mutation · Haplotype analysis
Introduction Dystrophinopathies are the most common form of muscular dystrophies caused by mutations in the dystrophin gene (DMD; OMIM 300,377) (Elhawary et al. 2018). It occurs in two types, including severe Duchenne muscular dystrophy (DMD;OMIM 310,200) with an incidence of 1 in Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13258-020-00975-z) contains supplementary material, which is available to authorized users. * Yongxin Ma [email protected] 1
Department of Medical Genetics, West China Medical School, West China Hospital, Sichuan University, 1st Keyuan 4 Lu, High‑Tech Zone, Chengdu 610041, Sichuan, China
3600–5000 live male births and relatively mild Becker muscular dystrophy (BMD; OMIM 300,376) with an incidence of 1 in 20,000 male births ( Yu et al. 2017; Zimowski et al. 2017; Elhawary et al. 2018). As a severe X-linked recessive muscle-wasting disease, DMD is characterized by pseudohypertrophy in the calf muscle and the ra
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