Our study was aimed to explore the clinical implication of chromosome microarray analysis (CMA) in genetically etiological diagnosis of children with congenital heart disease (CHD). A total of 104 children with CHD with or without multiple congenital anomalies (MCA) or intellectual disabilities/developmental delay (ID/DD) but normal karyotype were investigated using Affymetrix CytoScan HD array. Pathogenic copy number variations (PCNVs) were identified in 29 children (27.9%). The detection rates in children with simple CHD and complex CHD were 31.1% (19/61) and 23.2% (10/43), respectively. The detection rates of PCNVs were 17.9% (7/39), 20% (5/25), 63.2% (12/19) and 23.8% (5/21) in isolated CHD, CHD plus MCA, CHD plus ID/DD, CHD plus MCA and ID/DD, respectively. The PCNVs rate of CHD plus ID/DD was significantly higher than that of isolated CHD. Two genomic loci including 15q11.2 deletion and 1q43-q44 deletion were considered as CHD locus. The DVL1, SKI, STIM1, CTNNA3 and PLN were identified as candidate genes associated with CHD phenotypes. CMA can increase the diagnostic rate and improve the etiological diagnosis in children with CHD. We suggest CMA as a first-tier test in children with CHD, especially in children with CHD plus ID/DD.

(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.

α-Thalassemia is a common inherited disease in southern China. The severest form is Hb Bart's hydrops fetalis, in which the affected fetuses almost always die in utero or shortly after birth, and the mothers are at high risk for severe morbidity. Therefore, this condition should be controlled, especially prenatally. In this study, we reported on a two-year experience in prenatal control of Hb Bart's hydrops fetalis at a mainland Chinese hospital. Totally, 573 pregnancies at risk for Hb Bart's hydrops fetalis were referred and different prenatal procedures were offered depending on the gestational age at presentation. One hundred fifty-two affected fetuses were diagnosed prenatally; among these, only half presented in early gestation, and were terminated in time. Although our prenatal program has successfully prevented the birth of children with severe thalassemia, it does not show a satisfactory outcome, considering the gestational age when an affected pregnancy is terminated.

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.