Simultaneous CNV-seq and WES: An effective strategy for molecular diagnosis of unexplained fetal structural anomalies
Haoqing Zhang,
Xinglan He,
Yuankun Wang,
Caiyun Li,
Hongguo Jiang,
Shuai Hou,
Dongqun Huang,
Wenqian Zhang,
Jufang Tan,
Xiaoyun Du,
Yinli Cao,
Danjing Chen,
Haiying Yan,
Lingling Peng,
Dongzhu Lei
Affiliations
Haoqing Zhang
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Xinglan He
Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Yuankun Wang
BGI Genomics, Shenzhen, 518083, China; Clin Lab, BGI Genomics, Wuhan, 730074, China; Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, China
Caiyun Li
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Dongqun Huang
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Wenqian Zhang
BGI Genomics, Shenzhen, 518083, China; Clin Lab, BGI Genomics, Wuhan, 730074, China; Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, China
Jufang Tan
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Xiaoyun Du
Clin Lab, BGI Genomics, Wuhan, 730074, China; Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, China
Yinli Cao
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Danjing Chen
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Haiying Yan
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China
Lingling Peng
The Chenzhou Affiliated Hospital, Department of Gynecology and Obstetrics, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
Dongzhu Lei
Center of Prenatal Diagnosis, The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, 423000, China; Corresponding author. The Affiliated Chenzhou Hospital, Hengyang Medical School, University of South China, Chenzhou, China.
Background: Fetal structural anomalies are detected by ultrasound in approximately 3 % of pregnancies. Numerous genetic diagnostic strategies have been widely applied to identify the genetic causes of prenatal abnormalities. We aimed to assess the value of simultaneous copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) in diagnosing fetuses with structural anomalies. Methods: Fetuses with structural anomalies detected by ultrasound were included for eligibility. After genetic counseling, WES and CNV-seq were performed on DNA samples of fetuses and their parents. All detected variants were evaluated for pathogenicity according to ACMG criteria, with the final diagnosis was determined based on ultrasound results and relevant family history. Results: The diagnostic rate of 174 fetuses with prenatal ultrasound abnormalities was 26.44 %, higher than that achieved through either CNV or WES analysis alone. Furthermore, the highest diagnostic rate was observed in fetuses with multiple system anomalies, accounting for 50 % of the total diagnostic yield, followed by skeletal system anomalies at 45.45 %. Three cases with multiple system abnormalities were found to have a dual diagnosis of pathogenic CNVs and SNV variants, representing 1.72 % of the total cohort. 38 pregnant women in their third trimester of pregnancy (27 weeks+) participated in this study, and 23.68 % received a confirmed genetic diagnosis. Finally, 31 women (67.39 %) voluntarily terminated their pregnancy following the testing and extensive genetic counseling. Conclusions: Our study demonstrated that the simultaneous CNV-seq and WES analyses are beneficial for the molecular diagnosis of underlying unexplained structural anomalies in fetuses. This strategy is more efficient in elucidating prenatal abnormalities with compound problems, such as dual diagnoses. Furthermore, the simultaneous strategy has a shorter turnaround time and is particularly suitable for families with structural anomalies found in the third trimester of pregnancy.
