The yield of SNP microarray analysis for fetal ultrasound cardiac abnormalities.

BACKGROUND: Chromosomal microarray analysis (CMA) has emerged as a critical instrument in prenatal diagnostic procedures, notably in assessing congenital heart diseases (CHD). Nonetheless, current research focuses solely on CHD, overlooking the necessity for thorough comparative investigations encompassing fetuses with varied structural abnormalities or those without apparent structural anomalies. OBJECTIVE: This study sought to assess the relation of single nucleotide polymorphism-based chromosomal microarray analysis (SNP-based CMA) in identifying the underlying causes of fetal cardiac ultrasound abnormalities. METHODS: A total of 2092 pregnant women who underwent prenatal diagnosis from 2017 to 2022 were included in the study and divided into four groups based on the presence of ultrasound structural abnormalities and the specific type of abnormality. The results of the SNP-Array test conducted on amniotic fluid samples from these groups were analyzed. RESULTS: Findings from the study revealed that the non-isolated CHD group exhibited the highest incidence of aneuploidy, overall chromosomal abnormalities, and trisomy 18, demonstrating statistically significant differences from the other groups (p < 0.001). Regarding the distribution frequency of copy number variation (CNV) segment size, no statistically significant distinctions were observed between the isolated CHD group and the non-isolated CHD group (p > 0.05). The occurrence rates of 22q11.2 and 15q11.2 were also not statistically different between the isolated CHD group and the non-isolated congenital heart defect group (p > 0.05). CONCLUSION: SNP-based CMA enhances the capacity to detect abnormal CNVs in CHD fetuses, offering valuable insights for diagnosing chromosomal etiology and facilitating genetic counseling. This research contributes to the broader understanding of the utility of SNP-based CMA in the context of fetal cardiac ultrasound abnormalities.

Case Report: Prenatal Diagnosis of a Fetus With Harlequin Ichthyosis Identifies Novel Compound Heterozygous Variants: A Case Report.

BACKGROUND: Harlequin ichthyosis (HI) is the most severe form of the keratinizing disorders, and it is characterized by whole-body hard stratum corneum. ABCA12 has been identified as the major disease-causing gene of HI. METHODS: A case of HI was prenatally diagnosed by ultrasonography and genetic tests. The fetus had been found with dentofacial deformity and profound thickening of the palm and plantar soft tissues. Chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were then performed on the amniotic fluid to identify germline pathogenic variants for the fetus. Candidate variants were verified by Sanger sequencing. RESULTS: Compound heterozygous frameshift variants (p.Q719QfsX21; p.F2286LfsX6) of ABCA12 were identified for the fetus, suggesting the former variants were maternally inherited and the latter paternally inherited. The fetus was terminated. CONCLUSION: A prenatal molecular diagnosis is an important approach for the prevention of HI. In the study, we provided a successful case of genetic counseling for a family with an HI baby.

[Phenotypic and genetic analysis of a sibpair with partial deletion of SATB2 gene caused by 2q33.1 microdeletion].

OBJECTIVE: To analyze the genotype and phenotype of a sibpair with partial deletion of SATB2 gene caused by 2q33.1 microdeletion. METHODS: Both children have featured mental retardation and development delay, and were subjected to karyotyping, single nucleotide microarray (SNP array) and real-time fluorescence quantitative PCR analysis. Karyotyping and SNP Array analysis were also carried out on their parents to verify the origin of mutation. RESULTS: Both sibs had a normal karyotype. SNP array showed that sib 1 had arr[hg19]2q33.1(200 192 328 - 200 197 269)×1 (4.9 kb), 2q35 (218 105 663 - 218 816 675)×3 (711 kb), while sib 2 had arr[hg19]2q33.1(200 192 328 - 200 197 269)×1 (4.9 kb), 2q35 (218 105 663-218 810 908)×3 (705.2 kb). The deletion has partially overlapped with that of 2q33.1 microdeletion syndrome and involved part of the SATB2 gene. The result of real-time fluorescence quantitative PCR assay was consistent with that of SNP assay. The duplication has originated from their father and has not been associated with any disease phenotypen. CONCLUSION: Both sibs have carried partial deletion of SATB2 gene and had similar clinical phenotypes. Haploinsufficiency of such gene probably underlies the clinical manifestations in both patients.

Comparison of Efficiencies of Non-invasive Prenatal Testing, Karyotyping, and Chromosomal Micro-Array for Diagnosing Fetal Chromosomal Anomalies in the Second and Third Trimesters.

In this study, we aimed to compare the efficiency of non-invasive prenatal testing (NIPT), karyotyping, and chromosomal micro-array (CMA) for the diagnosis of fetal chromosomal anomalies in the second and third trimesters. Pregnant women, who underwent amniocenteses for prenatal genetic diagnoses during their middle and late trimesters, were recruited at the Prenatal Diagnosis Center of Taizhou City. Maternal blood was separated for NIPT, and amniotic fluid cells were cultured for karyotyping and CMA. The diagnostic efficiency of NIPT for detecting fetal imbalanced anomalies was compared with karyotyping and CMA. A total of 69 fetal chromosomal imbalances were confirmed by CMA, 37 were diagnosed by NIPT and 35 were found by karyotyping. The sensitivities of NIPT and karyotyping for diagnosing aneuploidy were 96.3% and 100% respectively. Only one mosaic sexual chromosome monosomy was misdiagnosed by NIPT, whereas the sensitivity of NIPT and karyotyping was 70% and 30%, respectively, for detecting pathogenic deletions and duplications sized from 5-20 Mb. Taken together, our results suggest that the efficiency of NIPT was similar to the formula karyotyping for detecting chromosome imbalance in the second and third trimesters.

[Application of BACs-on-Beads and karyotyping for the prenatal diagnosis of 1371 pregnant women with a high risk].

OBJECTIVE: To assess the value of combined BACs-on-BeadsTM (BoBs) and chromosomal karyotyping for the diagnosis of women with high-risk pregnancy. METHODS: For 1371 women with singleton pregnancy and various indications for prenatal diagnosis, karyotyping and BoBs were simultaneously applied on their amnionic fluid samples. RESULTS: In total 23 cases of trisomy 21, 11 cases of trisomy 18, 5 cases of sex chromosome aneuploidies, 6 cases of microdeletions/microduplications, 2 cases of chimeric chromosomes and 1 case of structural chromosomal abnormality were detected by the BoBs assay, among which the 6 microdeletions/microduplications were not detected by karyotyping. Karyotyping analysis has identified an extra yield of 19 chromosomal abnormalities and 34 chromosomal polymorphisms. CONCLUSION: Combined use of BoBs and chromosomal karyotyping can improve the detection rate of fetal chromosomal abnormalities including microdeletions/microduplications, which should find a wider use in the clinics.