• Genes and Genomics
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• v.40 no.12
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• pp.1339-1349
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• 2018

Cerebral palsy (CP) is a non-progressive neurological disease, of which susceptibility is linked to genetic and environmental risk factors. More and more studies have shown that CP might be caused by multiple genetic factors, similar to other neurodevelopmental disorders. Due to the high genetic heterogeneity of CP, we focused on investigating related molecular pathways. Ten children with CP were collected for whole-exome sequencing by next-generation sequencing (NGS) technology. Customized processes were used to identify potential pathogenic pathways and variants. Three pathways (axon guidance, transmission across chemical synapses, protein-protein interactions at synapses) with twenty-three genes were identified to be highly correlated with CP. This study showed that the three pathways associated with CP might be the molecular mechanism of pathogenesis. These findings could provide useful clues for developing pathway-based pharmacotherapies. Further studies are required to confirm potential roles for these pathways in the pathogenesis of CP.

• Journal of Genetic Medicine
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• v.5 no.1
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• pp.7-14
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• 2008

Twenty years have passed since a prenatal screening for Down syndrome and neural tube defect was applied to obstetric field. The Quad test (AFP, hCG, uE3, Inhibin-A) of the second trimester and the combination test (PAPP-A, hCG, NT) of the first trimester became popular now. The recent trend of prenatal screening is to combine these two screening tests together in order to increase a detection rate of Down syndrome. Three types of screening methods are introduced as follows; integrated test, sequential test and contingent test. In addition to combination of each test, an incorporation of characteristic ultrasound findings of Down syndrome is suggested for its risk calculation. The absence of fetal nasal bone would be a very useful marker especially in the first trimester screening test. According to a change of way calculating risk of Down syndrome, obstetrician's role will be more increased not by passive participation, but by active participation using ultrasound in risk calculation.

• Journal of Genetic Medicine
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• v.15 no.2
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• pp.72-78
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• 2018

Purpose: Physicians' attitudes may have a strong influence on women's decision regarding prenatal screening options. The aim of this study is to assess the physicians' attitudes toward prenatal screening for fetal aneuploidy including non-invasive prenatal testing (NIPT) in South Korea. Materials and Methods: Questionnaires were distributed and collected at several obstetrics-gynecological conferences and meetings. The questionnaire included 31 multiple choice and 5 fill-in-the-blank questions. Seven questions requested physicians' demographic information, 17 questions requested information about the NIPT with cell-free fetal DNA, and 12 questions requested information about general prenatal screening practices. Results: Of the 203 obstetricians that completed the survey. In contrast with professional guidelines recommending the universal offering of aneuploidy screening, only 53.7% answered that prenatal aneuploidy testing (screening and/or invasive diagnostic testing) should be offered to all pregnant women. Physicians tended to have positive attitudes toward the clinical application of NIPT as both primary and secondary screening methods for patients at high-risk for fetal trisomy. However, for patients at average-risk for fetal trisomy, physicians tended to have positive attitudes only as a secondary screening method. Physicians with more knowledge about NIPT were found to tend to inform their patients that the detection rate of NIPT is higher. Conclusion: This is the first study to investigate expert opinion on prenatal screening in South Korea. Education of physicians is essential to ensure responsible patient counseling, informed consent, and appropriate management after NIPT.

• Journal of Genetic Medicine
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• v.18 no.2
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• pp.117-120
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• 2021

We experienced a case of Xq deletion -- 46,X,del(X)(q22.3) -- detected by abnormal noninvasive prenatal screening, subsequently diagnosed by amniocentesis. Genetic counseling was a challenge because there are few reports of prenatal diagnosis of Xq deletion. In each female cell, one X chromosome is inactivated at random early in development, and there may be a preferential inactivation of the abnormal X chromosome. But some proportions of genes escape inactivation. The most common manifestation in women with Xq deletion is primary or secondary ovarian failure. Critical regions for ovarian function may be located at the long arm of the X chromosome. But, the onset and the severity of ovarian failure may vary with diverse, intricate factors. We anticipate that noninvasive prenatal screening can identify the broader range of chromosomal or genetic abnormalities with the advances in technology and analytic methods. We report our case with a brief review of the literature.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.72-78
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• 2015

Recently, noninvasive prenatal test (NIPT) has been adopted as a primary screening tool for fetal chromosomal aneuploidy. The principle of NIPT lies in isolating the fetal fraction of cell-free DNA in maternal plasma and analyzing it with bioinformatic tools to measure the amount of gene from the target chromosome, such as chromosomes 21, 18, and 13. NIPT will contribute to decreasing the need for unnecessary invasive procedures, including amniocentesis and chorionic villi sampling, for confirming fetal aneuploidy because of its higher positive predictive value than that of the conventional prenatal screening method. However, its greater cost than that of the current antenatal screening protocol may be an obstacle to the adoption of this innovative technique in clinical practice. Digital polymerase chain reaction (dPCR) is a novel approach for detecting and quantifying nucleic acid. dPCR provides real-time diagnostic advantages with higher sensitivity, accuracy, and absolute quantification than conventional quantitative PCR. Since the groundbreaking discovery that fetal cell-free nucleic acid exists in maternal plasma was reported, dPCR has been used for the quantification of fetal DNA and for screening for fetal aneuploidy. It has been suggested that dPCR will decrease the cost by targeting specific sequences in the target chromosome, and dPCR-based noninvasive testing will facilitate progress toward the implementation of a noninvasive approach for screening for trisomy 21, 18, and 13. In this review, we highlight the principle of dPCR and discuss its future implications in clinical practice.

• The Journal of the Korea Contents Association
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• v.15 no.3
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• pp.252-264
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• 2015

The purpose of this study was to identify pregnant women's needs for information on prenatal genetic diagnosis and screening. This study is consisted of two phases. In the first phase in December 2011, six blogs featuring questions and answers on prenatal genetic diagnosis and screening were selected from four major search engines in Korea by using the keywords "prenatal genetic diagnosis," "prenatal genetic screening", and "amniocentesis." An analyzing framework was constructed on the basis of 389 posts on six blogs between November 2006 and October 2011. In the second phase, the contents of the "MomsHolicbaby" blog posted from November 2010 to October 2011 were reviewed. Then, pregnant women's questions on prenatal genetic diagnosis and screening (100 questions) and amniocentesis (200 questions with 1,665 answers) were analyzed using descriptive statistics. Among posters who had ever been recommended to undergo amniocentesis, 56.5% described feelings of anxiety, 25.5% did not know the purpose of the test, and 33.9% refused to undergo the test. Among 295 posters answering questions about amniocentesis, 61.4% disagreed with undergoing the test. The results show that there is a need for healthcare professionals to provide more educational and emotional support to pregnant women considering prenatal genetic diagnosis and screening. Providing online health information can be integrated into prenatal genetic education for pregnant women as well as nurses. In addition, prenatal women's preferences about undergoing amniocentesis should be reflected in the current legal discussion on criteria for termination of pregnancy.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.66-71
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• 2015

Down syndrome screening with cell-free DNA (cfDNA) in the maternal plasma has recently received much attention in the prenatal diagnostic field. Indeed, a large amount of evidence has already accumulated to show that screening tests with cfDNA are more sensitive and specific than conventional maternal serum and/or ultrasound screening. Globally, more than 1,000,000 of these noninvasive prenatal tests (NIPTs) have been performed to date. There are several different methods for NIPTs that are currently commercially available, including shotgun massively parallel sequencing, targeted massively parallel sequencing, and single nucleotide polymorphism (SNP)-based methods. All of these methods have their own advantages and disadvantages. In this review, I will focus specifically on the SNP-based NIPT.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.85-91
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• 2015

Purpose: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. Materials and Methods: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. Results: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. Conclusion: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.

• Journal of Genetic Medicine
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• v.14 no.1
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• pp.1-7
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• 2017

Purpose: The aim of this study was to assess the diagnostic efficacy of noninvasive prenatal screening for trisomy 18 by assessing the levels of unmethylated-maspin (U-maspin) and fetal nuchal translucency (NT) thickness during the first trimester of pregnancy. Materials and Methods: A nested case-control study was conducted using maternal plasma samples collected from 65 pregnant women carrying 11 fetuses with trisomy 18 and 54 normal fetuses. We compared the U-maspin levels, NT thicknesses, or a combination of both in the first trimester between the case and control groups. Results: U-maspin levels and NT thickness were significantly elevated in the first trimester in pregnant women carrying fetuses with trisomy 18 when compared to those carrying normal fetuses (27.2 vs. 6.6 copies/mL, P<0.001 for U-maspin; 5.9 vs. 2.0 mm, P<0.001 for NT). The sensitivities of the U-maspin levels and NT thickness in prenatal screening for fetal trisomy 18 were 90.9% and 90.9%, respectively, with a specificity of 98.1%. The combined U-maspin levels and NT thickness had a sensitivity of 100% in prenatal screening for fetal trisomy 18, with a specificity of 98.1%. Conclusion: A combination of U-maspin levels and NT thickness is highly efficacious for noninvasive prenatal screening of fetal trisomy 18 in the first trimester of pregnancy.

• The Journal of Korean Academic Society of Nursing Education
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• v.19 no.4
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• pp.675-683
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• 2013

Purpose: Nineteen articles were analyzed to gather opinions and nursing implications about NIPT recently launched. Methods: Nineteen articles were selected from EBSCO (eBook business collection), Google Scholar, and two Korean academic d-bases with key words 'prenatal screening testing', 'prenatal genetic diagnostic testing', NIPT or 'cell free DNA (cfDNA)'. Authors developed a framework for analyzing the 19 articles including opinions and suggestions for future implications. Results: Eleven articles written by the first author affiliated with medicine or genetics, viewed NIPT as promising because of safety, accuracy, early detectability and cost effectiveness. Articles written by journalists or authors affiliated with history and ethics were concerned with the possible risk of ELSI (ethical, legal, social issues), erratic interpretation of test results, and lack of genetic counseling service. Conclusion: With consideration of Korean clinical, and legal circumstances, not only pregnant women and families but also health professionals must prepare for clinical NIPT implications including updating prenatal genetic testing, counseling services, protecting ELSI and amulticultural team approach.