Centre for Gene and Protein Research, Hanoi Medical University, Hanoi, Viet Nam.
Centre for Gene and Protein Research, Hanoi Medical University, Hanoi, Viet Nam.
Taiwan J Obstet Gynecol. 2019 Sep;58(5):645-649. doi: 10.1016/j.tjog.2019.07.011.
Duchenne Muscular Dystrophy is an X-linked recessive disorder characterized by progressive muscular degeneration, patients often develop cardiac failure in the later stage and death occurs before 20 years of age. For a disease with poor postnatal prognosis such as Duchenne Muscular Dystrophy (DMD), providing the carrier mother with the option of prenatal diagnosis in a subsequent pregnancy is accepted practice in many places where termination of pregnancy is allowed. Though methods of direct sequencing such as Sanger's sequencing has been widely used, Next-Generation Sequencing is been increasingly replacing most of its application. For the DMD gene, being the longest gene in the human genome, methods of direct sequencing is often unpractical and time-consuming, instead, STR analysis for linkage analysis would be a cost-effective option and have been used routinely for prenatal diagnosis of DMD. The diagnostic significance of the STRs is based on several criteria, the most important one being the heterozygosity of the locus, power of discrimination (PD) and power of exclusion (PE).
In this study, we investigated the feasibility of application and diagnostic value of 6 STR loci (DSTR49, DSTR50, DXS1036, DXS1067, DXS890, DXS9907) in the proximity of the DMD gene, 66 healthy individuals were recruited for STR analysis and 5 cases of prenatal diagnosis for carrier mother were performed.
Allele frequency, heterozygosity, polymorphic information content, the power of discrimination and exclusion and Hardy-Weinberg equilibrium were analyzed and calculated for the 6 STR loci. 5 of these loci (DSTR49, DSTR50, DXS1067, DXS890, DXS9907) were found practical and useful for preimplantation Genetic diagnosis (PGD) and prenatal diagnosis. All 5 cases of prenatal diagnosis using the method had informative STR results and correct diagnosis.
We concluded that our protocol of STR analysis can be applied for prenatal diagnosis and pre-implantation genetic diagnosis of DMD with high confidence and accuracy, especially in clinical settings where diagnostic resources are more limited.
杜氏肌营养不良症是一种 X 连锁隐性遗传病，其特征是进行性肌肉退化，患者常在后期发展为心力衰竭，20 岁前死亡。对于杜氏肌营养不良症（DMD）等预后不良的疾病，在允许终止妊娠的地方，为携带者母亲提供后续妊娠的产前诊断选择是被接受的做法。尽管直接测序方法（如 Sanger 测序）已被广泛应用，但下一代测序技术正越来越多地取代其大部分应用。对于 DMD 基因，它是人类基因组中最长的基因，直接测序方法通常不切实际且耗时，相反，连锁分析的 STR 分析将是一种具有成本效益的选择，并已被常规用于 DMD 的产前诊断。STR 的诊断意义基于几个标准，最重要的是基因座的杂合性、鉴别力（PD）和排除力（PE）。
在这项研究中，我们研究了 DMD 基因附近的 6 个 STR 基因座（DSTR49、DSTR50、DXS1036、DXS1067、DXS890、DXS9907）的应用可行性和诊断价值，招募了 66 名健康个体进行 STR 分析，并对 5 例携带者母亲进行了产前诊断。
分析和计算了 6 个 STR 基因座的等位基因频率、杂合度、多态信息含量、鉴别力和排除力以及 Hardy-Weinberg 平衡。其中 5 个基因座（DSTR49、DSTR50、DXS1067、DXS890、DXS9907）被认为在植入前遗传学诊断（PGD）和产前诊断中具有实际和有用性。使用该方法的所有 5 例产前诊断均获得了有信息的 STR 结果和正确的诊断。
我们的 STR 分析方案可用于 DMD 的产前诊断和植入前遗传学诊断，具有高度的信心和准确性，特别是在诊断资源更为有限的临床环境中。
