Chromosome Deletion ; Chromosome Disorders ; diagnosis ; genetics ; therapy ; Chromosomes, Human, Pair 22 ; genetics ; Female ; Humans ; Infant

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) for prenatal diagnosis. METHODS: G-banding karyotyping and CMA were simultaneously performed on 546 women who were subjected to amniocentesis during middle pregnancy. RESULTS: In total 82 cases were detected with chromosomal abnormalities. The two methods were consistent in 43 cases, which included 14 trisomy 21, 6 trisomy 18, 1 trisomy 13, 14 sex chromosomal aneuploidies, 4 chromosomal deletions, 3 chromosomal duplications and 1 sex chromosomal mosaicism. Fifteen fetuses with chromosomal abnormalities detected by CMA were missed by karyotyping analysis, which included 9 microdeletions and 6 microduplications. Sixteen fetuses with chromosomal abnormalities detected by karyotyping analysis were missed by CMA, which included 15 chromosomal translocations and 1 sex chromosomal mosaicism. In 7 cases, the results of karyotyping analysis and CMA were inconsistent. One supernumerary marker chromosome detected by karyotyping analysis was verified by CMA as 9p13.1p21.1 duplication. CONCLUSION Combined chromosomal karyotyping and CMA can significantly improve the detection rate for chromosomal abnormalities, which has a great value for prenatal diagnosis.
Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; genetics ; Female ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo assess the value of combined BACs-on-Beads(BoBs) and chromosomal karyotyping for the diagnosis of women with high-risk pregnancy.

METHODSFor 1371 women with singleton pregnancy and various indications for prenatal diagnosis, karyotyping and BoBs were simultaneously applied on their amnionic fluid samples.

RESULTSIn total 23 cases of trisomy 21, 11 cases of trisomy 18, 5 cases of sex chromosome aneuploidies, 6 cases of microdeletions/microduplications, 2 cases of chimeric chromosomes and 1 case of structural chromosomal abnormality were detected by the BoBs assay, among which the 6 microdeletions/microduplications were not detected by karyotyping. Karyotyping analysis has identified an extra yield of 19 chromosomal abnormalities and 34 chromosomal polymorphisms.

CONCLUSIONCombined use of BoBs and chromosomal karyotyping can improve the detection rate of fetal chromosomal abnormalities including microdeletions/microduplications, which should find a wider use in the clinics.

Adult ; Chromosome Aberrations ; Chromosome Disorders ; genetics ; Female ; Humans ; Karyotyping ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; methods

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the analysis of 824 samples from miscarriage or stillbirth. METHODS: Copy number variations (CNVs) in the abortic chorionic villi or stillbirth tissues were detected by CMA. RESULTS: All specimens were successfully analyzed, among which 381 (46.2%) were diagnosed with chromosomal abnormalities, which included 312 (81.9%) numerical abnormalities, 66 (17.3%) structural abnormalities and 3 (0.8%) uniparental disomies. Among numerical chromosomal abnormalities, aneuploidies was most common (92.0%), with trisomy 16 and 45,X accounting for 41 (13.1%) and 63 (20.2%) of the cases, respectively. Among the 66 structural chromosomal aberrations, there were 26 (39.4%) CNVs duplications, 20 (30.3%) CNVs deletions, and 20 (30.3%) CNVs duplication and deletions. 33 CNVs were predicted as have a high chance to lead to a disease. CONCLUSION CMA is a reliable, robust, and high-resolution method for the analysis of miscarriage or stillbirth samples. Numerical aberrations, in particular chromosomal aneuploides, are the main cause for spontaneous abortions and stillbirths.
Abortion, Spontaneous ; genetics ; Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Microarray Analysis ; Pregnancy ; Stillbirth ; genetics

OBJECTIVETo explore the application of combined techniques for the prenatal diagnosis of a case with 7q11.23 duplication.

METHODSAmniocentesis was performed in the second trimester for a mother with a high risk suggested by serological prenatal screening. G-banded chromosomal analysis was performed on cultured amniocytes and peripheral blood samples from both parents. DNA from amniotic fluid sample was isolated for a BACs-on-Beads (BoBs) assay. To define the range of duplication, copy number variation was determined with single nucleotide polymorphism array (SNP array, Affymetrix CytoScan 750K) and fluorescence in situ hybridization (FISH) analysis.

RESULTSChromosomal analysis suggested that the fetus and both parents all had a normal karyotype, while a duplication of 7q11.23 was detected by the BoBs assay. SNP array revealed a 1.5 Mb duplication in chromosome 7q11.23, which was confirmed by FISH.

CONCLUSIONCombined prenatal BoBs, SNP array and FISH has enabled effective diagnose of a case with 7q11.23 syndrome.

Adult ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; genetics

OBJECTIVETo assess the value of chromosome microarray analysis (CMA) for identifying the etiology of patients with congenital cleft lip and palate.

METHODSTwenty-two patients with no identifiable chromosomal aberrations by conventional cytogenetic technique were selected. DNA was extracted and hybridized with Affymetrix CytoScan(TM) HD arrays following the manufacturer's protocol. The data were analyzed with a CHAS v2.0 software.

RESULTSCMA analysis has identified submicroscopic copy number variants (CNVs) in all of the cases, which have ranged from 100 kb to 1.8 Mb. Potential pathogenic CNVs were identified in 5 patients (22.7%), which involved microdeletions and microduplications on 8p23.1, 10q22.2-q22.3, 6q26, 20p12.1 and 18q12.3. MYST4, MACROD2 and SOX7 genes are likely the causative genes.

CONCLUSIONCMA is an effective method for identification of etiology in patients with cleft lip and palate. CMA should be provided for patients with cleft lip and palate but a normal karyotype. Especially for those with additional structural abnormalities, there is a high risk for submicroscopic chromosomal aberrations.

Child ; Child, Preschool ; Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; genetics ; Cleft Lip ; diagnosis ; genetics ; Cleft Palate ; diagnosis ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Infant ; Male ; Microarray Analysis

OBJECTIVEThis study was conducted on a patient with ring-chromosome 13 syndrome and the results were presented and comparatively analyzed with reference to the related literature so as to detect the correlation between chromosome 13 band and the phenotype.

METHODSIn this study the authors used G-banding, C-banding, N-banding, high-resolution banding, phenotype location analysis, and a comparative review of literature.

RESULTSIt was found that karyotypes of the patient's parents are normal. The patient's karyotype is 45, XX, -13/46, XX, r(13)/46, XX, r(13;13)/47, XX, 2r(13) (p13q32.3). The typical syndrome of ring-chromosome 13 is related to the deletion of 13q34; the deletion of 13q32-13q32.2 is related to hand and foot abnormality, heart murmur, renal defect, skeletal abnormality and external genital abnormality; the deletion of 13q32.3-13q33 is related to micrognathia; 13q22-13q32 is related to atresia, and 13q13-q22 is related to anencephaly.

CONCLUSIONIt is confirmed that a new breakage-reunion point of ring-chromosome is located at 13p13 and 13q32.3. The variety of clinical characteristics and phenotypes in patients with ring-chromosome 13 syndrome are closely related to the differences of the deletion of chromosome 13.

Chromosome Aberrations ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; genetics ; Chromosomes, Human, Pair 13 ; genetics ; Humans ; Infant ; Karyotyping ; Male ; Phenotype ; Review Literature as Topic ; Ring Chromosomes

OBJECTIVETo evaluate value of spectral karyotyping (SKY) in the detection of chromosomal abnormalities.

METHODSA total of 17 metaphase chromosome samples were investigated by SKY, including 10 normal and 5 balanced translocation samples of peripheral blood lymphocytes, one der(Y) sample of peripheral blood lymphocytes and one marker chromosome sample of amniotic fluid cells. The results were compared with those of G-banding diagnosis.

RESULTSTen normal and 5 balanced translocation samples were diagnosed successfully by SKY in accordance with the results of G-banding; furthermore, SKY analysis revealed that the der(Y) fragment originated from p-arm of chromosome 21 while the marker chromosome originated from chromosome 5.

CONCLUSIONSKY is a very sensitive and specific whole genome analysis tool for chromosomal abnormality diagnosis, and exceedingly valuable in the diagnosis on complex chromosomal abnormalities that can not be determined by G-banding.

Chromosome Aberrations ; Chromosome Banding ; methods ; Chromosome Disorders ; diagnosis ; genetics ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis ; methods ; Reproducibility of Results ; Sensitivity and Specificity ; Spectral Karyotyping ; methods

OBJECTIVE: To reported on two fetuses diagnosed with 17q12 microdeletion syndrome. METHODS: The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography. Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array (SNP-array) analysis. After 17q12 microdeletion was found in the first fetus, SNP-array was carried out on peripheral blood samples of the parents to determine its origin. With the medical history of the parents taken into consideration, the father underwent high-throughput sequencing for 565 urinary system-related genes to exclude pathogenic or likely pathogenic variants associated with congenital malformations of the urinary and reproductive systems. RESULTS: In both fetuses, SNP-array has revealed a 1.42 Mb deletion at 17q12, or arr[hg19]17q12 (34 822 465-36 243 365) × 1. In both cases the microdeletion was inherited from the father, in whom no urinary disease-related pathogenic or likely pathogenic variants was identified. CONCLUSION Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios. SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.
Chromosome Deletion ; Chromosome Disorders ; Chromosomes, Human, Pair 17 ; Female ; Fetus ; Genetic Counseling ; Genetic Testing ; Humans ; Polyhydramnios/genetics* ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies. METHODS: Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n = 83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n = 188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison. RESULTS: The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P < 0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83) vs. 5.32%(10/188)](P < 0.05). CONCLUSION CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Pregnancy, High-Risk ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Chromosome Disorders/genetics*