Chen Min, Chen Jingsi, Wang Chunli, Chen Fei, Xie Yinong, Li Yufan, Li Nan, Wang Jing, Zhang Victor Wei, Chen Dunjin
Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.
Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou, 510150, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China; Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes.
Eur J Obstet Gynecol Reprod Biol. 2020 Aug;251:119-124. doi: 10.1016/j.ejogrb.2020.04.033. Epub 2020 May 20.
To evaluate the clinical application of medical exome sequencing (MES) for prenatal diagnosis of genetic diseases related to fetal structural anomalies detected by prenatal ultrasound examination.
A total of 105 fetuses with structural anomalies were negative results in both Quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray analysis (CMA). Then trio-based MES was further used for identifying the potential monogenic diseases in these fetuses. Coding regions and known pathogenic non-coding regions of over 4000 disease-related genes were interrogated, and variants were classified following the guidelines of American College of Medical Genetics (ACMG).
The 105 fetuses with structural anomalies were categorized into 12 phenotypic groups. A definitive diagnosis was achieved in 19% (20/105) of the cases, with the identification of 21 pathogenic or likely pathogenic variants in 14 genes. The proportion of patients with diagnostic genetic variants varied between the phenotypic groups, with the highest diagnostic yield in the cardiovascular abnormalities (44%), followed by the skeletal and limb abnormalities (38%) and brain structural abnormalities (25%). In addition, 12 fetuses were detected variants of unknown significance (VOUS), while the relevance of phenotypes and variants would further evaluated.
MES can identify the underlying genetic cause in fetal structural anomalies. It can further assist the management of pregnancy and genetic counseling. It was demonstrated the importance of translating prenatal MES into clinical practice.
评估医学外显子组测序（MES）在产前诊断与产前超声检查发现的胎儿结构异常相关的遗传疾病中的临床应用。
共有105例有结构异常的胎儿在荧光定量聚合酶链反应（QF-PCR）和染色体微阵列分析（CMA）中结果均为阴性。然后采用基于三联体的MES进一步鉴定这些胎儿中潜在的单基因疾病。对4000多个疾病相关基因的编码区和已知致病非编码区进行检测，并按照美国医学遗传学学会（ACMG）的指南对变异进行分类。
105例有结构异常的胎儿被分为12个表型组。19%（20/105）的病例获得了明确诊断，在14个基因中鉴定出21个致病或可能致病的变异。诊断性遗传变异患者的比例在各表型组之间有所不同，心血管异常组的诊断率最高（44%），其次是骨骼和肢体异常组（38%）和脑结构异常组（25%）。此外，检测到12例胎儿有意义未明的变异（VOUS），而表型与变异之间的相关性将进一步评估。
MES可以识别胎儿结构异常的潜在遗传原因。它可以进一步协助孕期管理和遗传咨询。证明了将产前MES转化为临床实践的重要性。
