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Shi X.,Liaoning Medical University | Zhang Z.,Liaoning Medical University | Cram D.S.,Berry Genomics | Liu C.,Liaoning Medical University
Clinica Chimica Acta | Year: 2015

Background: Noninvasive prenatal testing (NIPT) by massively parallel sequencing (MPS) of the circulating cell free fetal (cff) DNA during the second trimester of pregnancy is now a frontline test for detecting common fetal chromosomal abnormalities. However, the availability of an earlier test result in the first trimester would enable better clinical management of high-risk pregnancies. The aim of the study was to determine the feasibility of early gestational NIPT. Methods: Plasma DNA libraries were subjected to MPS and chromosomal read counts normalized to reference. Chromosomal aneuploidy was determined by z-scores (- 3. <. z<. 3, normal range). The cff DNA fraction in 96 male pregnancies was calculated by the relative proportion of Y chromosomal reads. Results: NIPT results were obtained in the first (8-12. weeks) and second (15-18. weeks) trimester for 182 high-risk women. NIPT identified T21, T13 and 45,X in 3 pregnancies that were confirmed by karyotyping, but missed a T15 pregnancy that eventually miscarried. In the remaining 178 pregnancies, results for first and second trimester NIPT were normal. The median fetal fraction in the first trimester was 7.6 ± 4.18% and 15% of samples were identified with a cff fraction below 4%. Different trends of cff DNA fraction change were observed between the first and second trimester, with 59% of pregnancies showing an increase, 17% showing no change and 24% showing a decrease. Conclusions: Although NIPT was highly reliable and accurate at an earlier gestational age, clinical implementation should proceed with caution due to a small, but significant, number of pregnancies associated with a low cff DNA fraction. © 2014 Elsevier B.V. Source

Zhu X.,Nanjing Medical University | Li J.,Nanjing Medical University | Ru T.,Nanjing Medical University | Wang Y.,Nanjing Medical University | And 5 more authors.
Prenatal Diagnosis | Year: 2016

Objective: To determine the type and frequency of pathogenic chromosomal abnormalities in fetuses diagnosed with congenital heart disease (CHD) using chromosomal microarray analysis (CMA) and validate next-generation sequencing as an alternative diagnostic method. Method: Chromosomal aneuploidies and submicroscopic copy number variations (CNVs) were identified in amniocytes DNA samples from CHD fetuses using high-resolution CMA and copy number variation sequencing (CNV-Seq). Result: Overall, 21 of 115 CHD fetuses (18.3%) referred for CMA had a pathogenic chromosomal anomaly. In six of 73 fetuses (8.2%) with an isolated CHD, CMA identified two cases of DiGeorge syndrome, and one case each of 1q21.1 microdeletion, 16p11.2 microdeletion and Angelman/Prader Willi syndromes, and 22q11.21 microduplication syndrome. In 12 of 42 fetuses (28.6%) with CHD and additional structural abnormalities, CMA identified eight whole or partial trisomies (19.0%), five CNVs (11.9%) associated with DiGeorge, Wolf-Hirschhorn, Miller-Dieker, Cri du Chat and Blepharophimosis, Ptosis, and Epicanthus Inversus syndromes and four other rare pathogenic CNVs (9.5%). Overall, there was a 100% diagnostic concordance between CMA and CNV-Seq for detecting all 21 pathogenic chromosomal abnormalities associated with CHD. Conclusion: CMA and CNV-Seq are reliable and accurate prenatal techniques for identifying pathogenic fetal chromosomal abnormalities associated with cardiac defects. © 2016 John Wiley & Sons, Ltd. Source

Liu S.,Southern Medical University | Song L.,Southern Medical University | Cram D.S.,Berry Genomics | Xiong L.,Southern Medical University | And 7 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2015

Objectives To compare the performance of traditional G-banding karyotyping with that of copy number variation sequencing (CNV-Seq) for detection of chromosomal abnormalities associated with miscarriage. Methods Products of conception (POC) were collected from spontaneous miscarriages. Chromosomal abnormalities were detected using high-resolution G-banding karyotyping and CNV sequencing. Quantitative fluorescent polymerase chain reaction analysis of maternal and POC DNA for short tandem repeat (STR) markers was used to both monitor maternal cell contamination and confirm the chromosomal status and sex of the miscarriage tissue. Results A total of 64 samples of POC, comprising 16 with an abnormal and 48 with a normal karyotype, were selected and coded for analysis by CNV-Seq. CNV-Seq results were concordant for 14 (87.5%) of the 16 gross chromosomal abnormalities identified by karyotyping, including 11 autosomal trisomies and three sex chromosomal aneuploidies (45,X). Of the two discordant results, a 69,XXX polyploidy was missed by CNV-Seq, although supporting STR marker analysis confirmed the triploidy. In contrast, CNV-Seq identified a sample with 45,X karyotype as a 45,X/46,XY mosaic. In the remaining 48 samples of POC with a normal karyotype, CNV-Seq detected a 2.58-Mb 22q deletion associated with DiGeorge syndrome and nine different smaller CNVs of no apparent clinical significance. Conclusions CNV-Seq used in parallel with STR profiling is a reliable and accurate alternative to karyotyping for identifying chromosome copy number abnormalities associated with spontaneous miscarriage. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Source

Sun L.-M.,Fudan University | Sun L.-M.,Tongji University | Sun L.-M.,Shanghai Institute of Planned Parenthood Research | Li Y.,Tongji University | And 7 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2016

Objective: In monochorionic diamniotic (MCDA) twin pregnancies, unequal placental sharing does not always lead to adverse outcomes. The aim of this study is to investigate how unequal placental sharing may be compensated by placental anatomical changes.Methods: Between January 2012 and July 2013, a total of 60 uncomplicated MCDA pregnancies ending in live birth of healthy twins were studied. Placentas were divided into two groups; an equally shared placenta group (placenta territory discordance ≤25%, N = 40) and an unequally shared placenta group (placenta territory discordance >25%, N = 20). Angioarchitecture, cord insertion type and the distance between two cord insertions were compared.Results: Vascular anastomoses were seen in all 60 placentas, and 58 placentas (96.7%) had arterioarterial anastomoses (AA). The overall diameter of the AA was larger in the unequally shared placenta group as compared to the equally shared placentas (0.27 ± 0.12 cm versus 0.19 ± 0.1 cm, p < 0.05). The distance between the cord insertions was shorter in the unequally shared group (14.5 ± 6.0 cm versus 18.3 ± 6.5 cm, p < 0.05).Conclusion: The absence of adverse outcomes in unequally shared placenta group can be explained by the presence of large AA and shorter distance between cord insertions, protecting the twin with the smaller placental part against growth restriction and other pathology. © 2015 Informa UK Ltd. Source

Chai X.,Zhengzhou University | Ren P.,Zhengzhou University | Wei B.,Zhengzhou University | Ma J.,Zhengzhou University | And 4 more authors.
Clinica Chimica Acta | Year: 2016

Background: Plasma based EGFR mutation analysis is emerging as a viable alternative to tumour tissue genotyping for patients with non-small cell lung carcinoma (NSCLC). The purpose of the study was to determine the degree of concordance between EGFR genotypes derived from matching tissue and blood samples. Methods: EGFR activating mutations L858R, exon 19 deletions, G719A/C/S and L861Q as well as resistance mutations T790M and exon 20 insertions were co-analysed in 61 matching tissue and blood biopsies collected from NCSLC patients. Tissue and plasma genotyping was performed by amplification refractory mutation system PCR (ARMS-PCR) and circulating single molecule amplification and re-sequencing technology (cSMART), respectively. Results: Of the 61 paired samples, 44 (72.1%) were fully concordant, 2 (3.3%) were partially concordant and 15 (24.6%) were discordant for EGFR genotypes. The discordance was bidirectional with tissue and plasma failing to reveal the equivalent mutation in eight and nine cases, respectively. Benchmarking against ARMS-PCR tissue biopsy results as the gold standard, the sensitivity and concordance rates for plasma mutation detection by cSMART assay were 72.7% and 90.2% (L858R), 72.7% and 86.9% (exon 19 deletions) and 100% and 98.4% (T790M). Conclusions: The cSMART assay was highly reliable and accurate for plasma EGFR genotyping. Based on discordance trends, tumour heterogeneity was suspected to be the major factor preventing a concordant diagnosis in matching samples. © 2016 Elsevier B.V. Source

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