Li Huanzheng, Xu Chenyang, Mao Yijian, Lu Jinfang, Xiang Yanbao, Xu Xueqin, Tang Shaohua
Center of Prenatal Diagnosis, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018 Apr 10;35(2):169-174. doi: 10.3760/cma.j.issn.1003-9406.2018.02.005.
To establish individualized prenatal diagnosis program for families affected with Duchenne/Becker muscular dystrophy (DMD/BMD) and different clinical background using a variety of methods.
Multiplex ligation-dependent probe amplification (MLPA) was performed on 50 patients suspected for DMD/BMD. For single exon deletions of the DMD gene, PCR was used for validating the results. For those without any deletion or duplication, Sanger sequencing was used to screen for DMD gene mutations in the children and their mothers. Prenatal genetic testing was provided to female carriers using chorionic villus, amniocentesis or cord blood samples. To ensure the accuracy of diagnosis, all prenatal specimens were also subjected to linkage analysis.
Among the 50 patients with DMD/BMD, 23 harbored large deletions, 11 only had single exon deletions, 10 harbored duplications, and 5 had small scare mutations. No mutation was detected in one family. For 37 women undergoing prenatal diagnosis, 10 fetuses were identified as affected males, 6 were female carriers, while 21 were not found to carry any mutation. Testing of creatine kinase was consistent with the results of prenatal diagnosis. For a patient harboring exon 51 deletion, the same mutation was found in a fetus but not in their mother. The proband and fetus had inherited the same haplotype, which suggested that the mother probably has germline mosaicism for the mutation.
Application of individualized methods for analyzing pregnant women with different clinical background can minimize the risk for giving birth to further children affected with DMD/BMD.
运用多种方法为患有杜氏/贝克氏肌肉营养不良症（DMD/BMD）且临床背景各异的家庭建立个体化的产前诊断方案。
对50例疑似DMD/BMD的患者进行多重连接依赖探针扩增（MLPA）检测。对于DMD基因的单外显子缺失，采用聚合酶链反应（PCR）验证结果。对于无任何缺失或重复的患者，采用桑格测序法筛查患儿及其母亲的DMD基因突变。利用绒毛取样、羊膜穿刺术或脐带血样本为女性携带者提供产前基因检测。为确保诊断准确性，所有产前样本均进行连锁分析。
在50例DMD/BMD患者中，23例存在大片段缺失，11例仅有单外显子缺失，10例存在重复，5例有小的散在突变。1个家庭未检测到突变。在37例接受产前诊断的女性中，10例胎儿被鉴定为患病男性，6例为女性携带者，21例未发现携带任何突变。肌酸激酶检测结果与产前诊断结果一致。对于1例存在外显子51缺失的患者，在其胎儿中发现相同突变，但其母亲未发现。先证者和胎儿继承了相同的单倍型，这表明母亲可能存在该突变的生殖系嵌合体。
应用个体化方法分析不同临床背景的孕妇可将生育更多患DMD/BMD患儿的风险降至最低。
