Clinical and genetic characteristics of female dystrophinopathy carriers
Clinical and genetic characteristics of female dystrophinopathy carriers
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女性肌营养不良症携带者的临床和遗传特征
DOI：
10.3892/mmr.2019.9982
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Lan, Dan
中科院分区：
文献类型：
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作者：
Zhong, Jingzi;Xie, Yanshu;Lan, Dan
本研究旨在确定Duchenne型肌营养不良（DMD）/Becker型肌营养不良（BMD）显性携带者和有DMD/BMD家族史的无症状携带者的遗传状态，并确定潜在的简单可靠的方法来筛查肌营养不良症携带者。收集和分析可能携带者和MC的临床数据。MCs接受了肌营养不良蛋白基因外显子的多重连接依赖性探针扩增（MLPA），并结合基于下一代测序（NGS）平台的肌肉疾病面板测试。此外，根据先证者的突变，通过MLPA或桑格测序确定可能携带者的状态。共调查154名女性，其中78例为携带者，包括4例MC和74例无症状女性携带者。4个MCs存在重复突变。在74例无症状携带者中，41.89%携带有缺失突变，其中2例疑似生殖系嵌合型，而dystrophin基因无突变; 44.59%携带有外显子点突变，10例（13.51%）携带有重复突变。肌酸激酶（CK）受试者工作特征（ROC）曲线下面积为0.822，敏感性为65.38%，特异性为92.1%。DMD与CK、谷丙转氨酶、谷草转氨酶呈正相关。肌营养不良蛋白基因外显子的MLPA，沿着NGS和桑格测序，对于MCs的诊断和确定可能携带者的状态是有效的。ROC曲线分析也表明CK水平是区分DMD/BMD携带者的良好预测指标。
The present study aimed to determine the genetic status of manifesting carriers (MCs) of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) and asymptomatic carriers with a family history of DMD/BMD, and identify potential simple and reliable methods for screening dystrophinopathy carriers. Clinical data from probable carriers and MCs were collected and analyzed. MCs underwent multiplex ligation-dependent probe amplification (MLPA) for dystrophin gene exons combined with muscle disease panel test based on a next-generation sequencing (NGS) platform. In addition, the status of probable carriers was determined by MLPA or Sanger sequencing, according to the mutations of probands. A total of 154 female were enrolled, among which 78 cases were found to be carriers, including 4 MCs and 74 asymptomatic female carriers. The 4 MCs exhibited duplication mutations. Among the 74 asymptomatic carriers, 41.89% harbored deletion mutations, including 2 cases with suspected germline mosaicism and no mutation in the dystrophin gene, while 44.59% harbored point mutations in exons and only 10 cases (13.51%) carried duplication mutations. The area under the receiver operating characteristic (ROC) curve of creatine kinase (CK) was 0.822, with a sensitivity of 65.38% and specificity of 92.1%. In addition, DMD was positively correlated with the CK, alanine transaminase and aspartate transaminase levels of the carriers. MLPA for exons of the dystrophin gene, along with NGS and Sanger sequencing, was effective for the diagnosis of MCs and for determining the status of probable carriers. The ROC curve analysis also demonstrated that CK level was an excellent predictor for distinguishing DMD/BMD carriers.