(1) Objective: To investigate the prenatal diagnosis and genetic counseling for 16p11.2 microdeletion syndrome and to evaluate its pregnancy outcome. (2) Methods: This study included 4968 pregnant women who selected invasive prenatal diagnoses from 1 January 2017 to 1 August 2022. These 4698 pregnancies underwent chromosomal microarray analysis (CMA), data on 81 fetuses diagnosed with 16p11.2 microdeletion syndrome based on prenatal ultrasound features and genetic test results were recorded, and their pregnancy outcome was evaluated. (3) Results: 1.63% of fetuses (81/4968) were diagnosed with 16p11.2 microdeletion syndrome. Among these, there were skeletal malformations in 48.15% of the 81 fetuses, cardiovascular malformations in 30.86%, central nervous system malformations (CNS) in 11.11%, digestive system structural abnormalities in 6.17%, and isolated ultrasonography markers in 3.70%. (4) Conclusions: 16p11.2 microdeletion syndrome can display various systemic ultrasound abnormalities in the perinatal period but vertebral malformations are the most common. Our study is the first to report that TBX1 and CJA5 are associated with 16p11.2 microdeletion syndrome, expanding the disease spectrum of 16p11.2 microdeletion syndrome. In our study, the ventricular septal defect is the main feature of cardiac structural abnormalities caused by 16p11.2 microdeletion syndrome. In addition, our study highlights the use of CMA in 16p11.2 microdeletion syndrome, analyzed their genetic results, and evaluated the follow-up prognosis, which can be useful for prenatal diagnosis and genetic counseling.

Background: There are few studies on the detection rate by chromosomal microarray analysis (CMA) of the prenatal diagnosis of talipes equinovarus (TE) compared to conventional karyotyping. We aimed to explore the molecular etiology of fetal TE and examine the detection rate by CMA, which provides more information for the clinical screening and genetic counseling of TE. Methods: In this retrospective study, pregnancies diagnosed with fetal TE were enrolled and clinical data for all cases were retrieved from our medical record database, including demographic data for pregnancies, ultrasound findings, karyotype/CMA results, and pregnant and perinatal outcomes. Results: Among the 164 patients, 17 (10.4%) clinically significant variants were detected by CMA. In 148 singleton pregnancies, the diagnostic rate of clinically significant variants was significantly higher in the non-isolated TE group than in the isolated TE group (10/37, 27.0% vs. 6/111, 5.4%, P < 0.001). In twin pregnancies, 1 (6.3%) pathogenic copy number variant was present in the other 16 twin pregnancies. Conclusions: This study demonstrates that CMA is useful for the prenatal genetic diagnosis of fetal TE. Fetal TE with the associated structural malformation correlates with a higher probability of clinically significant variants. This data may aid prenatal diagnosis and genetic counseling for fetal TE.

Background: There are few studies on the burden of chromosomal abnormalities and single gene disorders in fetal hemivertebra (HV). We aim to investigate the cytogenetic and monogenic risk and evaluate prenatal outcomes of fetal HV. Method: This study included fetuses diagnosed with HV divided into two groups: isolated HV and non-isolated HV. Data on other sonographic structural anomalies, chromosomal and sub-chromosomal abnormalities, monogenic variations detected by WES, and prenatal outcomes are recorded and reviewed. Results: Among 109 fetal HV cases, forty-seven (43.1%) non-isolated HV cases were associated with structural anomalies. Chromosomal test results were available in 58 cases, identifying six (10.3%) chromosomal aberrations involved in four isolated and two non-isolated HV. WES identified four (likely) pathogenic variants in three cases among 16 fetuses with HV, involving three novel variants, 1250G > T and c.1277G> inherited from parents, respectively, in DLL3 and c.7213C > A ** in the FLNB. The live birth rate (LB) was higher in the isolated fetal HV group than in the non-isolated group (67.7% (42/62) vs. 12.5% (12/47), p < 0.001). Conclusion: This study emphasizes the risk of cytogenetic abnormalities in isolated HV. WES yields a diagnostic rate of 18.3% in HV with normal CMA, probably aiding the prenatal counseling and management of fetal HV.

Currently, there are still many challenges in prenatal diagnosis, such as limited or uncertain fetal phenotyping, variant interpretation, and rapid turnaround times. The aim of this study was to illustrate the value of a comprehensive genomic evaluation in prenatal diagnosis. We retrospectively reviewed 20 fetuses with clinically significant copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) and no further exome sequencing testing in our tertiary center between 2019 and 2020. The residual DNA from the prenatal cases was used for the parallel implementation of CNV sequencing (CNV-seq) and trio-based clinical exome sequencing (trio-CES). CMA revealed 26 clinically significant CNVs (18 deletions and eight duplications) in 20 fetuses, in which five fetuses had two or more CNVs. There were eight fetuses with pathogenic CNVs (e.g., del 1p36), nine fetuses with likely pathogenic CNVs (e.g., dup 22q11.21), and three fetuses with variants of unknown significance (VOUS, e.g., dup 1q21.1q21.2). Trio-CES identified four fetuses with likely pathogenic mutations (SNV/InDels). Of note, a fetus was detected with a maternally inherited hemizygous variant in the SLX4 gene due to a 16p13.3 deletion on the paternal chromosome. The sizes of CNVs detected by CNV-seq were slightly larger than that of the SNP array, and four cases with mosaic CNVs were all identified by CNV-seq. In conclusion, microdeletion/duplication syndromes and monogenic disorders may co-exist in a subject, and CNV deletion may contribute to uncovering additional recessive disease alleles. The application of a comprehensive genomic evaluation (CNVs and SNV/InDels) has great value in the prenatal diagnosis arena. CNV-seq based on NGS technology is a reliable and a cost-effective technique for identifying CNVs.

(1) Objective: To evaluate the application of chromosomal microarray analysis (CMA) in fetuses with pulmonary atresia (PA) and to explore the risk factors for predicting chromosomal imbalances and adverse perinatal outcomes. (2) Methods: This study investigated 428 cases of PA singleton pregnancies that were tested using CMA and quantitative fluorescent polymerase chain reaction (QF-PCR) as first-line genetic testing. The PA cases were divided into two groups: an isolated group and a non-isolated group. (3) Results: CMA revealed clinically relevant copy number variations (CNVs) in 9/139 (6.47%) PA fetuses, i.e., pathogenic copy number variations (pCNVs) in 8/139 (5.76%) fetuses and likely pathogenic CNVs in 1/139 (0.72%) fetuses. Stratified analysis showed that the incidence of clinically significant variants was higher in non-isolated PA fetuses than in isolated PA fetuses (12.50%, 6/48 vs. 3.30%, 3/91, p = 0.036). Regression analysis showed that a combination of other structural abnormalities at diagnosis of PA represented the principal risk factor for chromosomal imbalances (OR = 2.672). A combination of other structural abnormalities and a high maternal age increased the risk of adverse pregnancy outcomes in PA cases, including intrauterine fetal death (IUFD), termination of pregnancy (TOP), and preterm delivery. (4) Conclusions: The value of CMA for locating imbalanced genetic variations in fetuses with PA was highlighted by this study, particularly when combined with additional structural abnormalities.