• Journal of Microbiology and Biotechnology
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• v.20 no.6
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• pp.959-967
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• 2010

Down syndrome (DS) is an abnormality of the 21st chromosome that commonly occurs in children born to older women. Thus, amniotic fluid (AF) is usually collected from such women for prenatal diagnosis. This study analyzed human AF supernatants (AFS) using a mass spectrometric (MS) approach to search for candidate biomarkers of a DS pregnancy. The AFS were collected from older pregnant women at weeks 16-18 of their gestation by amniocentesis for cytogenetic analysis. The AFS from the pregnancies carrying DS (n=4) or chromosomally normal (n=6) fetuses, as revealed by the cytogenetic analysis, were then subjected to global protein profiling based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Affinity chromatography was also applied prior to the LC-ESI-MS/MS to minimize the masking effect of highly abundant albumin and immunoglobulin and thereby increase the diversity of the identified proteins. As a result, at least 30 new AFS proteins were identified and 44 AFS proteins were found to be differentially expressed between the DS and normal cases, where 6 of the proteins were unique to the DS cases and 11 were unique to the chromosomally normal cases. In addition, in the DS cases, 19 AFS proteins were downregulated and 8 were upregulated to varying degrees. A Western blot analysis confirmed the LC-ESI-MS/MS data, indicating that the combined detection of apolipoprotein A-II (apoA-II) and alpha-fetoprotein (AFP) could be a potential tool for diagnosing DS cases.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.151-155
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• 2007

Diagnosis and prevention of cytogenetics diseases are one of the most important parts in prenatal care. For that reason, it is necessary to examine birth defects. However, there is no reliable statistical data about birth defects in our country. In this study, the ratio of birth defects were determined by cytogenetics analysis and amniocentesis, in addition, the usefulness of amniocentesis was analyzed. The screening test and the triple marker test were conducted for 3,325 pregnant women of between 15 and 22 weeks gestation. Amniocentesis was performed for 170 pregnant women who were positive in the two tests, 184 women of advanced maternal age and 48 women with family history of chromosome aberrations. Among 419 women, 8 pregnant women who were positive in the triple marker test, 1 woman who close to the cut-off value in the triple marker test, 2 women with advanced maternal age and 1 woman who has history of chromosome aberration pregnance that was positive in cytogenetics analysis. The overall incidence of chromosomal aberration was 12 cases including 7 cases of Down's syndrome, 1 case of Patau syndrome, 1 case of Klinefelter syndrome, 1 case of Edward syndrome, 1 case of Robertsonian translocation and 1 case of XYY syndrome. These results show that amniocentesis for pregnant women who need chromosome test in prenatal cytogenetics analysis is very useful.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.3
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• pp.223-231
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• 2003

Objective: The aim of the present study was to evaluate the clinical efficiency of fluorescent in situ hybridization (FISH) in the prenatal diagnosis of chromosomal aneuploidy. Methods: We reviewed data of 268 cases to identify women undergoing genetic amniocentesis at cytogenetic laboratory, from January 2000 to December 2002. Amniotic fluid was submitted for both rapid FISH on uncultured interphase amniocytes using a commercially available DNA probe for chromosome 13, 18, 21, X, Y and standard karyotyping on cultured metaphase amniocytes. Results from FISH and full karyotype were compared. Results: There were 251 cases (84%) normal and 17 cases (16%) abnormal in FISH results. All 17 cases of trisomy 13, 18, 21 including two cases of mosaicism and sex chromosome aneuploidies which are detected by FISH were confirmed with conventional cytogenetics and there was no false positive result. Twenty two cases had karyotypically proven abnormalities that could not have been detected by the targeted FISH. Conclusion: Interphase FISH analysis of uncultured amniotic fluid cells has been shown to be an effective and reliable technique for rapid fetal aneuploidy screening during pregnancy as an adjunctive test to conventional cytogenetics.

• Journal of Genetic Medicine
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• v.5 no.2
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• pp.125-130
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• 2008

Propose: To analyze the indications and cytogenetic results of midtrimester amniocentesis. Material and Methods: This study reviewed 2,523 cases of midtrimester prenatal genetic amniocentesis performed at MizMedi Hospital between January 2000 and December 2007. Results: The most frequent indication for midtrimester amniocentesis was advanced maternal age (45.9%), followed by positive serum markers (29.9%). Chromosomal aberrations were diagnosed in 110 cases (4.4%), for which numerical aberration accounted for 38 cases (34.5%), structural aberration accounted for 65 cases (59.1%), and mosaicism accounted for 7 cases (6.4%). Among the autosomal aberrations, there were 20 cases of trisomy 21 and 8 cases of trisomy 18. With respect to structural aberrations, there were 14 cases of reciprocal translocation and 8 cases of robertsonian translocation. The frequencies of chromosomal aberrations according to the indication were highest in individuals with a family history of chromosome abnormality 14.0% (8/57) followed by previous congenital anomaly 5.9% (2/34). Conclusion: Midtrimester amniocentesis is an effective tool for prenatal diagnosis. Indications such as advanced maternal age, maternal serum markers, and ultrasound are important for predicting abnormal fetal karyotypes.

• Journal of Genetic Medicine
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• v.8 no.1
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• pp.35-43
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• 2011

Purpose: We evaluated indications for chorionic villus sampling (CVS), the positive predictive value of CVS for fetal chromosomal abnormalities, and the fetal loss rate after CVS at CHA Medical Center. Materials and Methods: We reviewed the medical records of 511 cases of CVS performed between 67 and 120 days of gestation for prenatal cytogenetic diagnosis from April 2000 to April 2010. Fetal karyotypes were obtained by direct and indirect culture methods. Results: The most common indications for CVS were abnormal ultrasonic findings including increased nuchal translucency (294/635, 46.3%). The positive predictive value of abnormal karyotyping according to indication for CVS was highest in cases with abnormal parental karyotypes (14/21, 66.7%). Mosaicism revealed by CVS comprised 3.1% of the sample (16/509). Amniocentesis revealed two cases of true mosaicism and 11 cases of confined placental mosaicism. The fetal loss rate within 4 weeks of the procedure was 1.2% (6/511). Conclusion: If CVS is performed by an expert clinician, it is a feasible and reliable procedure for prenatal genetic diagnosis. When CVS indicates mosaicism, the finding should be confirmed by amniocentesis to distinguish true mosaicism from confined placental mosaicism.

• Journal of Genetic Medicine
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• v.5 no.1
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• pp.47-54
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• 2008

Purpose : Fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells offers the opportunity for rapid screening of aneuploidies and has become an integral part of the current practice in many clinical cytogenetics laboratories. Here, we retrospectively analyzed the results of interphase FISH in 943 amniotic fluid samples and assessed the efficiency of FISH for rapid detection of aneuploidies. Methods : Interphase FISH for chromosome 13, 18, and 21 was performed in 943 consecutive amniotic fluid samples for rapid diagnosis of aneuploidies referred from 2004 to 2006. Karyotypes from standard cytogenetic analysis were compared to the FISH results. Results : A total of 45 chromosomal rearrangements (4.8%) were found after conventional cytogenetic analysis of the 943 amniotic fluid. After exclusion of known familiar chromosomal rearrangements and inversions (2.1%, 20/943), 2.7% (25/943) were found to have chromosomal abnormalities. Of this group, 0.7% (6/943) were chromosomal abnormalities not detectable by FISH and 2.0% (19/943) were numerical abnormalities detectable by FISH. All 14 cases of Down syndrome (Classic type, 13 cases; Robertsonian type, 1 case) and 5 cases of trisomy 18 were diagnosed and detected by FISH and there were no false-positive or -negative results (specificity and sensitivity=100%). Conclusion : The present study demonstrates that FISH can provide a rapid and sensitive clinical method for prenatal identification of chromosome aneuploidies. However, careful genetic counseling is essential to explain the limitations of FISH, including the inability to detect all chromosomal abnormalities and the possibilities of uninformative or false-negative results in some cases.

• Journal of Yeungnam Medical Science
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• v.22 no.2
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• pp.241-246
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• 2005

Constitutional trisomy 8 is a relatively rare aneuploidy; most identified cases are mosaic with a normal cell line. The phenotype is highly variable from apparently normal to severe disability. The proportion of abnormal cells is dramatically different between tissues and the severity of the phenotype is not directly related to the level of mosaicism. Therefore, it is very difficult to provide a definitive prognosis. We report here a case of constitutional trisomy 8 mosaicism with agenesis of the corpus callosum, congenital heart disease and micrognathia. The trisomy 8 cell line was not detected by prenatal cytogenetic study. This is the fourth reported case of constitutional trisomy 8 mosaicism in Korea.

• Journal of Genetic Medicine
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• v.5 no.2
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• pp.139-144
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• 2008

We report on two cases of pericentric inversion of X chromosome. The cases were found in a 40-year-old man with azoospermia and in a family of a 38-year-old pregnant woman. The first case with 46,Y,inv(X)(p22.1q27) had concentrations of LH, prolactin, estradiol, and testosterone that were within normal ranges; however, FSH levels were elevated. Testis biopsy revealed maturation arrest at the primary and secondary spermatocytes without spermatozoa. There were no microdeletions in the 6 loci of chromosome Y. For the second case, the cytogenetic study of thepregnant woman referring for advanced maternal age and a family history of inversion X chromosome was 46,X,inv(X)(p22.11q27.2). The karyotype of her fetus was 46,X,inv(X)(p22.1q27). Among other family members, the karyotypes of an older sister in pregnancy and her fetus were 46,X,inv(X)(p22.11q27.2), and 46,Y,?inv(X), respectively. The proband's father was 46,Y,inv(X)(p22.11q27.2). All carriers in the family discussed above were fertile and phenotypically normal. In addition, the ratio of inactivation of inv(X) by RBG-banding was discordant between the two sisters, with the older sister having only 4.1% of cells carrying inactivated inv(X) while the proband had a 69.5% incidence of late replicating inv(X). Therefore, we suggest that the cause of azoospermia in the first case might be related to inversion X chromosome with positional effect. Also, the family of the second case showing normal phenotype of the balanced inv(X) might be not affected any positional effect of genes.