OBJECTIVETo assess the value of single nucleotide polymorphism array (SNP array) for the study of fetuses with conotruncal defects (CTD) detected by echocardiography.

METHODSSNP array was carried out on 75 fetuses with sonographically detected CTD but a normal karyotype. The results were analyzed with ChAS software.

RESULTSPathogenic CNVs were detected in 7 (9.3%) of all cases. Variant of uncertain significance (VOUS) was detected in 2 (2.7%) cases. Benign CNVs were detected in 19 (25.3%) cases.

CONCLUSIONSNP array is an effective method for delineating the etiology of fetuses with CTD, particularly for those with a normal karyotype.

Objective To investigate the effect of maternal age,gestational weeks,numbers of previous spontaneous abortion and embryo gender on chromosomal abnormalities.Methods Bacs on Beads (BoBs) technology was used to detect the chromosome aneuploidy of 245 pregnant women with spontaneous abortion or stillbirth in Jinan Maternity and Child Care Hospital from January 2015 to December 2017 and to analyze the types of their chromosome abnormalities.Comparative analysis between different groups was carried out using Chi-square test.Results Karyotypes of all cases (n=245) were obtained using BoBs.Among them,113 had chromosome abnormalities (46.1％),including 66 autosomal aneuploidy (58.4％),26 sex chromosome aneuploidy (23.0％),seven autosomal partial trisomy (6.2％),five autosomal partial monomer (4.4％),seven triploid (6.2％),one complex triploid (0.9％) and one double trisomy (0.9％).Pregnant women aged over 35 had a higher incidence of chromosome abnormality than those under 35 [61.0％ (36/59) vs 41.4％ (77/186),x2=8.003,P＜0.05].The incidence of chromosome abnormality of women aborted in the first-trimester was also higher than those aborted in the second-trimester [48.5％ (99/204) vs 34.2％ (14/41),x2=4.634,P＜0.05].Moreover,male embryos were more likely to have chromosome abnormality than female ones [57.6％ (49/85) vs 40.0％(64/160),x2=6.483,P＜0.05)].However,there was no significant difference between gravidas with different times of spontaneous abortion (0,1 or ≥ 2,P＞0.05).Conclusions Chromosome abnormality is a major cause of spontaneous abortion,particularly in embryos with chromosome aneuploidy,partial trisomy,partial monomer and triploid.Advanced maternal age may increase the risk of chromosome abnormalities in pregnancies complicated with spontaneous abortion or stillbirth.

Objective:To explore the genetic basis for a fetus with nuchal cystic hygroma identified in the first trimester and cholecystomegaly identified in the middle trimester of pregnancy.Methods:A 27-year-old pregnant woman who had presented at the Antenatal Diagnostic Center of Jinan Maternal and Child Health Care Hospital on October 25, 2018 was selected as the study subject. Chorionic villus sampling was carried out in the first trimester for chromosomal karyotyping and SNP-Array analysis. Amniocentesis was carried out in the second trimester, and peripheral blood of the couple was collected at the same time. Trio whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:No abnormality was found by chromosomal karyotyping and SNP-Array, whilst high-throughput sequencing revealed that the fetus had harbored a heterozygous c. 7732A>T (p.K2578X) nonsense variant of the NIPBL gene. Following elected abortion, the autopsy results were consistent with features of Cornelia de Lange syndrome (CdLS). The same variant was detected in neither parents and was unreported in the literature. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as pathogenic (PVS1+ PS2+ PM2_Supporting+ PP3). Conclusion:The novel nonsense variant of the NIPBL gene probably underlay the genetic etiology of CdLS in this fetus. Above finding has also enriched the mutational spectrum of the NIPBL gene.