Wang Huanhuan, Xu Yan, Liu Xiaoqing, Wang Lei, Jiang Wenting, Xiao Bing, Wei Wei, Chen Yingwei, Ye Weiping, Ji Xing
Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
Prenat Diagn. 2017 Apr;37(4):356-364. doi: 10.1002/pd.5019. Epub 2017 Mar 6.
The objective of this study is to report 6-year clinical prenatal diagnosis experience of Duchenne muscular dystrophy (DMD)-affected families evaluated at a single prenatal diagnosis center in China and establish a reliable and rational prenatal diagnosis procedure for DMD families.
The prenatal diagnosis data of 146 at-risk pregnancies in 131 DMD families referred to our center from 2010 to 2016 were retrospectively reviewed.
The mutation detection rate of the probands was greater than 99%. In the 131 families, 50 mothers showed negative results during carrier testing, and de novo exon deletions arose in 51.1% of the probands. Of the 146 pregnancies, 91 were male fetuses, 34 of which were affected. Germline mosaicism was identified three times in this cohort, and recombination of the DMD gene was detected in nine cases.
Accurate genetic diagnosis of the proband is important for preventing recurrence in at-risk families. The present results demonstrate the importance of considering maternal germline mosaicism in the genetic assessment. Prenatal diagnosis should be suggested to the parent with a DMD proband whether carrier testing found the causative mutation in the mother's blood or not. Finally, we have developed a prenatal diagnosis algorithm for dystrophinopathies that combines multiplex ligation-dependent probe amplification, quantitative PCR, sequencing and linkage analyses. © 2017 John Wiley & Sons, Ltd.
本研究旨在报告在中国一家产前诊断中心对杜氏肌营养不良症（DMD）家系进行的6年临床产前诊断经验，并为DMD家系建立可靠且合理的产前诊断程序。
回顾性分析了2010年至2016年转诊至本中心的131个DMD家系中146例高危妊娠的产前诊断数据。
先证者的突变检出率大于99%。在131个家系中，50名母亲在携带者检测中结果为阴性，51.1%的先证者出现新发外显子缺失。在146例妊娠中，91例为男性胎儿，其中34例患病。在该队列中发现了3次生殖系嵌合体，9例检测到DMD基因重组。
先证者的准确基因诊断对于预防高危家系的复发很重要。目前的结果表明在基因评估中考虑母亲生殖系嵌合体的重要性。无论携带者检测是否在母亲血液中发现致病突变，均应向有DMD先证者的父母建议进行产前诊断。最后，我们开发了一种用于肌营养不良症的产前诊断算法，该算法结合了多重连接依赖探针扩增、定量PCR、测序和连锁分析。© 2017 John Wiley & Sons, Ltd.
