Outcomes of pregnancies with trisomy 16 mosaicism detected by NIPT: a series of case reports

Background Trisomy 16 (T16) is thought to be the most frequent chromosome abnormality at conception, which is often associated with a high risk of abnormal outcomes. Methods A retrospective analysis of 14 cases with high risk of T16 by noninvasive prenatal testing (NIPT) was conducted. All cases in the analysis involved prenatal diagnosis, karyotyping and chromosomal microarray analysis. Case reports NIPT detected 12 cases of T16 and 2 cases of T16 mosaicism. Prenatal diagnosis confirmed 5 true positive cases and 9 false positive cases. Among the 5 true positive cases, 3 cases had ultrasound abnormalities. All of the 9 false positive cases continued their pregnancies. The newborns who were from these 9 false positive cases except 1 case (case 7) had low birth weights (< 2.5 kg) and there were also 2 premature deliveries. Conclusion NIPT serves as a fast and early prenatal screening method, giving clues to chromosome abnormalities and providing guidance for managing pregnancy. Confined placental mosaicism in 16 pregnancies may be at higher risk for preterm delivery.

Analysis of NGS-Ministr as A New Detection Strategy Chromosomal Trisomy 16 of Fetal Materials in Miscarriages

Background: Although many technologies can identify chromosomal abnormalities, they can’t completely replace the advantages of short tandem repeat (STR) genotyping technology. The miniSTR typing based on next generation sequencing (NGS-miniSTR) with high throughput, accuracy and sensitivity has the potential to determine the trisomy and overcome the limitations of conventional STR techniques, which never be tried. The study aimed to explore the value of the NGS-miniSTR in trisomy testing, which is an extension and improvement of the methodology of chromosomal detection technology.Methods: A total of 140 fetal materials in miscarriages (70 trisomy 16 and 70 normal karyotypes) screened by copy-number variation sequencing (CNV-seq) were genotyped using the customed panel containing 11 miniSTRs based on NGS. Direct counting method, chi-square (χ2) test, k-means clustering analysis and Mahalanobis distance were operated to compare the difference of miniSTR between trisomy 16 and normal group, and then analyze whether trisomy 16 could be identified.Results: All miniSTR results based on NGS were successfully obtained, except for D16S771 in 21 samples. There were significant differences in the average depth of coverage at each locus in each sample. Direct counting method and chi-square (χ2) test showed significant differences in allelic pattern and read ratio between trisomy and normal group, respectively. Almost all samples correctly divided into 2 clusters based on diallelic STR reads ratios according to k-means clustering analysis. In addition, the Mahalanobis distance showed that D16S771 had multiple outliers. Conclusion: A new strategy of miniSTR-NGS was firstly introduced to successfully detect all samples of trisomy 16 in the fetal material in miscarriages, which revealed that the allelic pattern and allelic read ratio could be effective indexes to identify the number of chromosomes.

Pregnancy Outcomes in Trisomy 16 Mosaicism Pregnancies Detected by NIPT, A Series of Case Reports

Trisomy 16 s often associated with a high risk of abnormal outcome. A retrospective analysis of 14 cases with T16 high risk in NIPT, and all had undergone prenatal diagnosis, including karyotype and CMA. NIPT had detected 11 of T16, 2 of T16 mosaisism, and 1of more Chr. 16. Prenatal diagnosis confirmed 5 true positive cases and 9 false positive cases. In the 5 true positive cases, 3 out of 5 cases had ultrasound abnormality. In the 9 false positive cases, all the pregnancies continued. All the pregnancies were born with low weight (<2.5kg) except case 7. There were two pregnancies with premature, which suggested that CPM 16 pregnancies may be at higher risk for preterm delivery. NIPT could serve as a fast and early prenatal screening to provide guidance for pregnancy and termination of pregnancy is medically safer when it is performed in the earlier pregnancy.

Increased methylation of gene promoters in the trophoblast of spontaneous miscarriages with trisomy 16

Обнаружен повышенный уровень нарушений эпигенетической регуляции экспрессии генов в трофобласте хориона спонтанных абортусов с трисомией 16. Среди гиперметилированных генов была значимо обогащена группа генов секретируемых белков, значительное количество генов кодировали рецепторы и транскрипционные факторы. Гиперметилирование выявленных генов является потенциальной причиной гибели эмбрионов с трисомией 16 на ранних стадиях развития. An increased level of abnormal epigenetic regulation of gene expression in the trophoblast of spontaneous miscarriages with trisomy 16 was found. Among the hypermethylated genes, the group of genes of secreted proteins was significantly enriched, and a significant number of genes encoded receptors and transcription factors. Hypermethylation of the identified genes is a potential cause of death of embryos with trisomy 16 in the early stages of development.

Mosaic Trisomy 16 Associated with Left Lung Agenesis, Abnormal Left Arm, and Right Pulmonary Artery Stenosis: Expanding the Phenotype and Review of the Literature

Trisomy 16 is the most common autosomal trisomy found in spontaneous abortions with mosaic versions seen in survivors. However, surviving children have multiple congenital defects and are at risk of growth and developmental delay. We report an additional case of mosaic trisomy 16 diagnosed by amniocentesis and confirmed after birth. Our patient is the first documented case of living mosaic trisomy 16 with the malformation constellation of lung agenesis, left pulmonary artery agenesis, congenital heart defects, and ipsilateral radial ray and limb abnormalities, expanding the phenotype of this rare condition. Additionally, this individual's unique combination of lung and cardiac defects caused morbidities that were challenging to manage and complicated family counseling as well.

The Association of Clinical Characteristics With Cytogenetic Testing in Miscarriage Tissues: A Retrospective Review

Background It is known little about to what extent the cytogenetic abnormalities association with clinical factors including maternal age, history of miscarriage, fertilization way and ultrasonographic finding in miscarriage tissues. A comprehensive investigation had informed to reveal the relevance of the profiles of these clinical factors of miscarriage with chromosomal abnormalities and propose feasible recommendations. Methods 478 cases of miscarriage tissue were performed by chromosomal microarray analysis between January 1, 2019, and December 31, 2019, the collected clinical data and the genetic findings were assessed using chi-squared analysis. Results 261 cases (54.7%) were identified as chromosomal abnormalities. Trisomy took place more frequency in advanced age of pregnancy women (p＜0.05), and it was closely related to the history of miscarriage. trisomy 16 (24.1%) was predominant in the ＜35 years group, whereas trisomy 15 (25.0%) was significantly more frequent in ≥35 years group. Trisomy 16, 15 and 13 were significantly more frequent in the first miscarriage, the second miscarriage and more than two times miscarriage, respectively. The positive rate in more than two times miscarriage in＜35 years group and ≥35 years group was 40.9% and 87.5%, respectively. More than two times miscarriages in ＜35 years was significantly difference with ≥35 years (P=0.02). Conclusion It is necessary to perform cytogenetic analysis to the miscarriage cases which are considered about the maternal age combined with history of miscarriage.