scholarly journals The Application of Late Amniocentesis: A Retrospective Study in a Tertiary Fetal Medicine Center in China

2020 ◽  
Author(s):  
Yingting Li ◽  
Huanchen Yan ◽  
Jingsi Chen ◽  
Fei Chen ◽  
Wei Jian ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Genetic Test ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Test Results ◽  
Whole Exome ◽  
Genetic Test Results

Abstract Background: To assess the indications and complications of late amniocentesis, and the advantage of advanced genetic test results in a tertiary university fetal medical medicine unit.Methods: In this retrospective study, women that underwent amniocentesis at 24+0 to 39+4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy. Information was retrieved from patient medical records, checked by research staff, and analyzed. Results: Of the 1277 women (1311 fetuses) included, late detected sonographic abnormalities (86.2%) were the most common indication. The overall preterm birth and intrauterine demise rate were 2.6% and 1.2%, respectively, after amniocentesis. Sixty-six fetuses with aneuploidy (5.1%) and sixty-seven fetuses with pathogenic copy number variations (5.1%) were identified by chromosomal microarray analysis. One pathogenic copy number variation was detected by whole-exome sequencing. The maximal diagnostic yield (36.1%) was in the subgroup of fetuses with the abnormal noninvasive prenatal test, following by multiple abnormalities (23.8%). And 35.8% of the pregnancies were finally terminated.Conclusions: Due to the high detection rates of advanced genetic technologies and safety of the invasive procedure, it is reasonable to recommend late amniocentesis as an effective and credible method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Therefore, comprehensive genetic counseling is necessary.

scholarly journals The application of late amniocentesis: a retrospective study in a tertiary fetal medicine center in China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yingting Li ◽  
Huanchen Yan ◽  
Jingsi Chen ◽  
Fei Chen ◽  
Wei Jian ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Genetic Test ◽  
Late Onset ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Control Group ◽  
Chromosomal Microarray Analysis ◽  
Test Results ◽  
Detection Rates ◽  
Genetic Test Results

Abstract Background To assess the indications and complications of late amniocentesis and the advanced genetic test results in a tertiary university fetal medical medicine unit. Methods In this retrospective study, women that underwent amniocentesis at 24+ 0 to 39+ 4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy and compared with those who underwent the traditional amniocentesis at 16+ 0 to 23+ 6 weeks (control group). Information was retrieved from patient medical records, checked by research staff, and analyzed. Results Of the 1287 women (1321 fetuses) included in the late amniocentesis group, late detected sonographic abnormalities (85.5%) were the most common indication. The overall incidence of preterm birth and intrauterine demise after amniocentesis were 2.5 and 1.3%, respectively. Sixty-nine fetuses with aneuploidy (5.3%) and seventy-two fetuses with pathogenic copy number variations (5.5%) were identified by chromosomal microarray analysis. The maximal diagnostic yield (70%) was in the subgroup of fetuses with the abnormal diagnostic test results, followed by abnormal NIPT results (35.7%) and multiple abnormalities (23.8%). And 35.4% of the pregnancies were finally terminated. Conclusions Due to the high detection rates of advanced genetic technologies and the safety of the invasive procedure (3.9% vs 4.0%), it is reasonable to recommend late amniocentesis as an effective and reliable method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Comprehensive genetic counseling is necessary.

scholarly journals Whole Exome Sequencing Facilitated the Identification of a Mosaic Small Supernumerary Marker Chromosome (sSMC)

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Huan-xia Xing ◽  
Peng-bin Li ◽  
Li-min Cui ◽  
Jian-ye Jiang ◽  
Ning-ning Hu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Extended Family ◽  
Phenotypic Variability ◽  
Marker Chromosome ◽  
Chromosome 8 ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosomal Anomalies ◽  
Whole Exome

Small supernumerary marker chromosomes (sSMCs) are a group of rare chromosomal anomalies, which pose challenges in the clinical practice of prenatal diagnosis and genetic counseling. This study enrolled an extended family with an underage male patient displaying infantile seizures, intellectual disability, and retarded speech and psychomotor function. A series of multiplatform genetic detections was conducted to explore the diagnostic variation. Whole exome sequencing (WES) and chromosomal microarray analysis (CMA) indicated a mosaic sSMC derived from the pericentromeric region of chromosome 8 in the patient, which was confirmed using cytogenetic methods. The proband and his mother, who carried this mosaic variant, exhibited strong phenotypic variability. We also ruled out the pathogenicity of a KDM5C variant by extended validation. Our results emphasized the capacity of WES to detect mosaic SMCs and the importance of mosaic ratios in the appearance and severity of symptomatic phenotypes.

scholarly journals Genetic Analysis in Fetal Skeletal Dysplasias by Trio Whole-Exome Sequencing

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kai Yang ◽  
Ming Shen ◽  
Yousheng Yan ◽  
Ya Tan ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Inheritance ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Skeletal Dysplasias ◽  
Whole Exome ◽  
Quantitative Fluorescence

Skeletal dysplasias (SDs) comprise a series of severe congenital disorders that have strong clinical heterogeneity and usually attribute to diverse genetic variations. The pathogenesis of more than half of SDs remains unclear. Additionally, the clinical manifestations of fetal SDs are ambiguous, which poses a big challenge for accurate diagnosis. In this study, eight unrelated families with fetal SD were recruited and subjected to sequential tests including chromosomal karyotyping, chromosomal microarray analysis (CMA), and trio whole-exome sequencing (WES). Sanger sequencing and quantitative fluorescence PCR (QF-PCR) were performed as affirmative experiments. In six families, a total of six pathogenic/likely pathogenic variations were identified in four genes including SLC26A2, FGFR3, FLNB, and TMEM38B. These variations caused disorders following autosomal dominant or autosomal recessive inheritance patterns, respectively. The results provided reliable evidence for the subsequent genetic counseling and reproductive options to these families. With its advantage in variation calling and interpreting, trio WES is a promising strategy for the investigation of fetal SDs in cases with normal karyotyping and CMA results. It has considerable prospects to be utilized in prenatal diagnosis.

The Promise of Whole-exome Sequencing for Prenatal Genetic Diagnosis

2020 ◽  
Vol 17 (1) ◽  
pp. 25-31
Author(s):  
Jiun Kang
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Disorders ◽  
Genetic Diagnosis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Prognostic Information ◽  
Prenatal Genetic Diagnosis ◽  
Whole Exome ◽  
Nextgeneration Sequencing

Prenatal genetic diagnosis provides information for pregnancy and perinatal decision- making and management. Cytogenetic testing methods, including chromosomal microarray analysis and gene panels, have evolved to become a part of routine laboratory testing, providing valuable diagnostic and prognostic information for prenatal diagnoses. Despite this progress, however, cytogenetic analyses are limited by their resolution and diagnosis is only possible in around 40% of the dysmorphic fetuses. The advent of nextgeneration sequencing (NGS), whole-genome sequencing or whole-exome sequencing has revolutionized prenatal diagnosis and fetal medicine. These technologies have improved the identification of genetic disorders in fetuses with structural abnormalities and provide valuable diagnostic and prognostic information for the detection of genomic defects. Here, the potential future of prenatal genetic diagnosis, including a move toward NGS technologies, is discussed.

scholarly journals Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder

JAMA ◽  
2015 ◽  
Vol 314 (9) ◽  
pp. 895 ◽  
Author(s):  
Kristiina Tammimies ◽  
Christian R. Marshall ◽  
Susan Walker ◽  
Gaganjot Kaur ◽  
Bhooma Thiruvahindrapuram ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Diagnostic Yield ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Molecular Diagnostic ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Whole Exome

Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study

2014 ◽  
Vol 88 (1) ◽  
pp. 34-40 ◽  
Author(s):  
D.A. Dyment ◽  
M. Tétreault ◽  
C.L. Beaulieu ◽  
T. Hartley ◽  
P. Ferreira ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pediatric Epilepsy ◽  
Phenotypic Spectrum ◽  
Whole Exome

Whole-exome sequencing reveals potential germline and somatic mutations in 60 malignant ovarian germ cell tumors

2021 ◽  
Author(s):  
Juan Chen ◽  
Yan Li ◽  
Jianlei Wu ◽  
Yakun Liu ◽  
Shan Kang
Keyword(s):  
Germ Cell ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Peripheral Blood ◽  
Copy Number ◽  
Somatic Mutations ◽  
Germ Cell Tumors ◽  
Germline Mutations ◽  
Deletion Region ◽  
Whole Exome

Abstract Background Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. Methods The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes corresponding to copy number alterations (CNA) deletion and duplication region, functional annotation of was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region. Results In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YST). Moreover, POU5F1 was the most significant mutated gene with mutation frequency > 10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region) was found in 2 YST and nuclear staining in 2 dysgerminomas (DG) tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I-like receptor, Toll-like receptor, NF-kappa B and Jak–STAT. KRT4, RPL14, PCSK6, PABPC3 and SARM1 mutations were detected in both peripheral blood and tumor samples. Conclusions Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.

scholarly journals RefCNV: Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing

2016 ◽  
Vol 15 ◽  
pp. CIN.S36612 ◽  
Author(s):  
Lun-Ching Chang ◽  
Biswajit Das ◽  
Chih-Jian Lih ◽  
Han Si ◽  
Corinne E. Camalier ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Estimation Methods ◽  
Single Nucleotide Variants ◽  
False Positive Error ◽  
Reference Set ◽  
Genome Wide ◽  
Whole Exome

With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon. The construction of the reference set includes an evaluation of the sources of variability in the coverage distribution. We observed that the processing steps had an impact on the coverage distribution. For each exon, we compared the observed coverage with the expected normal coverage. Thresholds for determining CNVs were selected to control the false-positive error rate. RefCNV prediction correlated significantly ( r = 0.96–0.86) with CNV measured by digital polymerase chain reaction for MET (7q31), EGFR (7p12), or ERBB2 (17q12) in 13 tumor cell lines. The genome-wide CNV analysis showed a good overall correlation (Spearman's coefficient = 0.82) between RefCNV estimation and publicly available CNV data in Cancer Cell Line Encyclopedia. RefCNV also showed better performance than three other CNV estimation methods in genome-wide CNV analysis.

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