Chromosomal copy number analysis on chorionic villus samples from early spontaneous miscarriages by high throughput genetic technology

Shen, Jiandong; Wu, Wei; Gao, Chao; Ochin, Humphrey; Qu, Dianyun; Xie, Jiazi; Gao, Li; Zhou, Yadong; Cui, Yugui; Liu, Jiayin

doi:10.1186/s13039-015-0210-z

Cited by 47 publications

(56 citation statements)

References 21 publications

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“…The overall detection rate of clinically significant chromosomal abnormalities was 55.1% (295/535), and the rate of VOUS was 2.8%, which is in accordance with previous studies (6,7,9,15). We also compared the frequency and distribution of chromosomal abnormalities between patients with SA and RM.…”

Section: Discussionsupporting

confidence: 89%

Clinical application of SNP array analysis in first‐trimester pregnancy loss: a prospective study

Wang¹,

Cheng

Meng³

et al. 2016

Clinical Genetics

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Chromosomal microarray analysis (CMA) has been used routinely in pediatric and prenatal genetic diagnosis in clinical practice, but it has rarely been applied to miscarriage analysis. In this study, we conducted a prospective study to evaluate the feasibility of CMA for genetic diagnosis of first-trimester miscarriage specimens. We successfully analyzed 551 fresh miscarriage specimens using single-nucleotide polymorphism (SNP) array. Among the specimens, 2.9% (16/551) had significant maternal cell contamination and were excluded from the study. Clinically significant chromosomal abnormalities were identified in 295 (55.1%) cases, including 214 (40%) with aneuploidy, 40 (7.5%) with polyploidy, 19 (3.6%) with partial aneuploidy, 12 (2.2%) with pathogenic microdeletion/microduplication, and 10 (1.9%) with uniparental isodisomy (isoUPD). Variants of uncertain significance were obtained in 15 cases (2.8%). Notably, isoUPD involving a single chromosome (chromosome 22) and two recurrent copy number variations, 22q11.2 microdeletion and 7q11.23 microdeletion, were identified as probably to be associated with miscarriage. The frequency and distribution of genetic aberrations in the spontaneous abortion group was not significantly different from those in the recurrent miscarriage group. Our study suggests SNP array is a reliable, robust, and high-resolution technology for genetic diagnosis of miscarriage in clinical practice.

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Section: Discussionsupporting

confidence: 89%

Clinical application of SNP array analysis in first‐trimester pregnancy loss: a prospective study

Wang¹,

Cheng

Meng³

et al. 2016

Clinical Genetics

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“…New generation sequencing may contribute more to knowledge of the genetic pathogenesis of miscarriage, but it is currently only used experimentally, mainly because of its high costs …”

Section: Discussionmentioning

confidence: 99%

“…MLPA probe kits for all chromosomes is the most useful, especially during the first trimester when numerical aberrations involving all chromosomes (exept for chromosome 1) may occur . The use of a limited probe panel for chromosomes 13, 18, 21 and sex chromosomes only enabled the detection of around 20% of genetic abnormalities in first trimester pregnancy loss and a panel for chromosomes 13, 16, 18, 21, 22 and sex chromosomes –around 60% of abnormalities in comparison to all chromosomes testing . Trisomies 13, 18, 21 and sex chromosome abnormalities most frequently occur after 10 weeks of pregnancy; therefore, even limited probe panels (commercially available FISH or QF‐PCR sets) may be useful screening methods .…”

Section: Discussionmentioning

confidence: 99%

“…New generation sequencing may contribute more to knowledge of the genetic pathogenesis of miscarriage, but it is currently only used experimentally, mainly because of its high costs. 28,29,48 In cases of conventional karyotyping failure or detection of normal karyotype, molecular methods make a significant contribution to the identification of the genetic causes of miscarriage. 49 They are also useful to detect the origin of small supernumeratory marker chromosomes undetected by conventional karyotyping.…”

Section: Discussionmentioning

confidence: 99%

“…7,20 The use of a limited probe panel for chromosomes 13, 18, 21 and sex chromosomes only enabled the detection of around 20% of genetic abnormalities in first trimester pregnancy loss and a panel for chromosomes 13,16,18,21,22 and sex chromosomes -around 60% of abnormalities in comparison to all chromosomes testing. 48 Trisomies 13, 18, 21 and sex chromosome abnormalities most frequently occur after 10 weeks of pregnancy; therefore, even limited probe panels (commercially available FISH or QF-PCR sets) may be useful screening methods. 4,18,20 However, the effectiveness of these methods depends strictly on the probes used in the test.…”

Section: Discussionmentioning

confidence: 99%

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First trimester pregnancy loss: Clinical implications of genetic testing

Massalska

Zimowski

Bijok

et al. 2016

J of Obstet and Gynaecol

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Around 10-15% of pregnancies result in a spontaneous first trimester miscarriage, which is most frequently caused by chromosomal abnormalities, mainly aneuploidies. Genetic analysis of pregnancy loss includes conventional G-banding karyotyping and various molecular methods. Apart from variable methodological limitations, the effectiveness of genetic analysis depends on the type and quality of the tested sample. To improve the reliability of genetic testing, we present methods of appropriate collection and pre-laboratory preparation of chorionic villi from first trimester miscarriage. We also discuss issues of maternal cell contamination, placental mosaicism and reciprocal and Robertsonian translocations in the context of interpretation of the results and genetic counseling.

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Genetics of Early Miscarriages

Vaiman

2016

Encyclopedia of Life Sciences

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Early miscarriage or early pregnancy loss (EPL) is defined by an embryonic foetal loss occurring before 13 weeks of gestation. In this article, we focus on the genetics of this complex human disease from studies of human patients, sometimes including foetal losses occurring before 20 weeks. Most of the mouse studies on EPL are based on gene invalidation experiments having much wider and pleiotropic effects than a mere defect of implantation or placental development, and therefore they will not be analyzed here. In addition, many good reviews are already available on gene polymorphisms relevant to early miscarriage and are only briefly summarised here. We develop more in‐depth aspects connected to microRNA and copy number variations with EPL, issues that have been much less reviewed in the past. Key Concepts Early pregnancy loss is a complex multifactorial disease, leading to embryo loss in an estimated >70% of the fertilisation events in humans. Besides chromosome anomalies, detected by cytogenetics or CGH arrays (array‐based comparative genomic hybridisation), gene variants are associated with an increased risk of pregnancy loss. These genes may be regulators of immune response including cytokines, modulators of the coagulation cascade, equilibrators of the oxidative stress or, rarely, genes involved in chromosome segregation at meiosis or mitosis. Other genes may be found by genome‐wide association studies. Recent novel studies are developing on the impact of epigenetic regulators (essentially microRNAs) on miscarriages. These can be relevant markers to categorise gene expression deregulation in pregnancy losses.

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Chromosomal copy number analysis on chorionic villus samples from early spontaneous miscarriages by high throughput genetic technology

Cited by 47 publications

References 21 publications

Clinical application of SNP array analysis in first‐trimester pregnancy loss: a prospective study

Clinical application of SNP array analysis in first‐trimester pregnancy loss: a prospective study

First trimester pregnancy loss: Clinical implications of genetic testing

Genetics of Early Miscarriages

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