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

OBJECTIVE: To assess the value of combined copy number variation sequencing (CNV-seq) and chromosomal karyotyping for the diagnosis of amniocytic mosaicisms, in addition with a literature review. METHODS: Forty cases of amniocytic mosaicisms detected at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2021, in addition with 245 mosaicisms retrieved from 11 recent literature were evaluated in terms of detection rate, consistency rate, and pregnancy outcomes. RESULTS: The detection rate of amniocytic mosaicisms was 0.46% (40/8 621) in our center. And its consistency rate with chromosomal karyotyping was 75.0% (30/40). After genetic counseling, 30 (75.0%) couples had opted to terminate the pregnancy, 5 (12.5%) had decided to continue with the pregnancy, 3 (7.5%) fetuses were born alive, and 2 cases (5.0%) were lost in touch. By contrast, 245 cases (0.39%) of mosaicisms were identified among 63 577 amniotic samples, with a consistency rate of 62.8% (103/164) with other techniques. Among these, 114 cases (55.1%) were terminated, 75 (36.2%) were born alive, and 18 (8.7%) were lost during the follow up. CONCLUSION Combined CNV-seq and chromosomal karyotyping has a high value for the detection of amniotic mosaicisms.
Pregnancy ; Female ; Humans ; Mosaicism ; Chromosome Disorders/genetics* ; DNA Copy Number Variations ; Chromosome Aberrations ; Karyotyping ; Prenatal Diagnosis/methods*

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations. METHODS: Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs). RESULTS: The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis. CONCLUSION For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.
Chromosome Aberrations ; Chromosome Disorders/genetics* ; DNA Copy Number Variations ; Female ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome. METHODS: A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated. RESULTS: Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome. CONCLUSION The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.
Female ; Pregnancy ; Humans ; Chromosome Deletion ; DNA Copy Number Variations ; Chromosome Disorders/genetics* ; Kidney ; Fetus ; Microarray Analysis ; Prenatal Diagnosis