RESUMO
Objective:To investigate the indications for prenatal diagnosis and pregnancy outcomes of fetal Turner syndrome (TS) with different karyotypes.Methods:Clinical data of TS cases diagnosed by fetal karyotyping in the Prenatal Diagnostic Center of Guangzhou Women and Children′s Medical Center from January 1, 2010, to June 30, 2021, were analyzed retrospectively. According to the karyotyping results, these cases were divided into two groups: monosomy X (45,X) and non-monosomy X groups (including karyotypes of mosaic monosomy X, isochromosome X, X deletion, X rearrangement, pseudodicentric X, and mosaicism with Y or Y deletion). Chi-square test was used to compare the detection rate, indications for prenatal diagnosis, and pregnancy outcomes of the two groups, and the Bonferroni test was conducted for further pairwise comparisons between the subgroups. The Chi-square test (or Fisher's exact test) was used to compare the abnormal ultrasound signs. Mann-Whitney U test was used to compare the nuchal translucency (NT) thickness of the two groups. Results:(1) Invasive prenatal diagnosis was performed on 27 981 pregnancies, and 205 (0.73%) of them were diagnosed with TS, including 135 cases of monosomy X and 70 cases of non-monosomy X (44 with numerical sex chromosome abnormalities, and 26 with structural sex chromosome abnormalities). (2) Out of the 205 pregnancies, 164 (80.0%) had one indication for prenatal diagnosis, and 41 (20.0%) had multiple indications. The detection rate of fetal ultrasonographic abnormalities [85.2% (115/135)] in monosomy X cases was significantly higher than that of three other indications [positive serological screening for Down's syndrome: 67.3% (35/52); positive non-invasive prenatal testing (NIPT) for sex chromosome abnormality: 60.0% (15/25); and other indications (advanced maternal age, adverse pregnancy history and thalassemia genes carried by both parents): 5.2% (7/135); all P<0.05], and also higher than the figure in non-monosomy X cases [25.7% (18/70), χ 2=71.55, P<0.001]. In non-monosomy X cases, the detection rates of TS among cases with high-risk results from serological screening for Down's syndrome and NIPT for sex chromosome abnormality [54.7% (29/53) and 68.3% (28/41)] were higher than those of the other two indications [fetal ultrasonographic abnormalities: 25.7% (18/70), other indications: 14.3% (10/70); all P<0.05]. (3) Of the 133 pregnancies with fetal ultrasonographic abnormalities as the indication, 65 (48.9%) had one abnormal ultrasound sign, and 68 (51.1%) had multiple signs. Among the 95 cases with ultrasound abnormalities in the first trimester and 38 cases in the second or third trimester, the incidence of cystic hygroma and hydrops was significantly higher in monosomy X cases than in non-monosomy X cases [in the first trimester: 71.8% (61/85) vs 1/10, 34.1% (29/85) vs 0/10; in the second or third trimester: 73.3% (22/30) vs 0/8, 50.0% (15/30) vs 0/8; Fisher's exact test, all P<0.05]. NT thickness in monosomy X cases was greater than that of non-monosomy X cases [7.5 mm (1.0-17.4 mm) vs 1.7 mm (0.8-9.5 mm), Z=－5.25, P<0.001]. (4) Among the 72 pregnancies with indications other than ultrasound abnormalities, 68 underwent Down's syndrome screening and 61 underwent NIPT. The detection rates among the cases with positive results in Down's syndrome screening, NIPT for a sex chromosome abnormality, and other indications (advanced maternal age, adverse pregnancy history, and thalassemia genes carried by both parents) were 54.4% (37/68), 59.0% (36/61) and 22.2% (16/72), respectively ( χ 2=22.40, P<0.001). The detection rates of the cases with high-risk results from Down's syndrome screening and NIPT for sex chromosome abnormality were higher than that of the cases with other indications ( χ 2=18.77 and 15.40, both P<0.001). Of the 72 pregnancies, 19 (26.4%) were monosomy X and 53 (73.6%) were non-monosomy X, including 42 (58.3%) with chromosomal mosaicism. (5) Among the 205 cases of TS, 185 were successfully followed up (123 were monosomy X and 62 were non-monosomy X). There was one live birth in monosomy X cases (0.8%, 1/123) and 17 in non-monosomy X cases (27.4%, 17/62), and the difference was statistically significant ( χ2=33.22, P<0.001). Sixty-three TS cases with normal ultrasound findings were followed up (18 were monosomy X and 45 were non-monosomy X). In these cases, all 18 pregnancies with monosomy X and 32 (71.1%, 32/45) with non-monosomy X were terminated and the other 13 (28.9%, 13/45) cases of non-monosomy X were delivered. Of the 18 live births, one (non-monosomy X) was delivered at 36 weeks of gestation and the rest were born at term. Eleven cases of them were followed up. The height of one child with monosomy X was lower than the average height of children of the same age and sex by more than 2 standard deviations (－2 SD). The height of 10 children with non-monosomy X were between－1 SD and +3 SD among the children of the same age and gender. The mental and motor development were good in the 11 cases, and no other structural abnormalities were observed. The remaining seven cases refused to be followed up. Conclusions:Ultrasonographic abnormalities are the main indications of fetal TS with monosomy X, while positive Down's syndrome screening and positive NIPT for sex chromosome abnormality are indicators of non-monosomy X. The termination rate for pregnancies with monosomy X is higher than that for non-monosomy X.
RESUMO
Objective:To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus.Methods:Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children′s Medical Center and Qingyuan People′s Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal.Results:Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses.Conclusions:Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.
RESUMO
Objective To investigate the relationship between spontaneous miscarriage and embryonic chromosome abnormalities,and to evaluate the clinical application of karyotype analysis by chorionic villus cell culture. Methods The chorionic villus karyotype of 1983 cases of miscarriage from January 2010 to July 2016 in Guangzhou Women and Children′ s Mecical Center were analyzed retrospectively. The miscarried chorionic villi were obtained by curettage under sterilized condition. The chromosome specimens were prepared after chorionic villus cell culture. Karyotype analysis was performed by G-banding technique. Results In the 1983 samples, successful karyotype analysis was performed in 1770 cases, with the successful rate of 89.98%. Chromosomal abnormalities were found in 1038 cases (58.64%,1038/1770). Chromosomal structural abnormalities were found in 37 cases. The numeral abnormalities were more common than structural abnormalities, and most of the numeral abnormalities were aneupoidies. In turn, they were trisomy 16, 45,X, trisomy 22, trisomy 2, trisomy 21, trisomy 15. The most common structural abnormality was balanced translocation, including Robersonian translocation. Female embryoes accounted for 61.02%(1080/1770) miscarriages and for 57.4%(596/1770) of chromosomal abnormalities, while male embroyes acoounted for 61.02%(1080/1770),57.4%(596/1770)respectively. The proportion of female embryoes was higher than male embryoes. The median age of the patients was 30 years old(16-46 years old). As the maternal age increased, the proportion chromosomal abnormalities increased. The incidence of chromosomal abnormalities in the advanced age group (≥35 years) was 68.38%(240/351), which was significantly higher than that in the younger group (56.24% ,798/1419; χ2=17.10, P<0.01). Conclusions Embryonic chromosomal abnormalities are the most common cause of early spontaneous miscarriage. The abnormalities centralize in some karyotypes. There is certain relationship between maternal age and the incidence of miscarriage, as well as the embryonic gender. Chorionic villus cell culture and karyotype analysis are helpful in finding the cause of miscarriage and counsel the patients.
RESUMO
<p><b>OBJECTIVE</b>To evaluate the method of array-based comparative genomic hybridization (array-CGH) in identifying unbalanced chromosome aberrations.</p><p><b>METHODS</b>Four cases that could not be diagnosed by conventional cytogenetic technique were selected to undergo array-CGH analysis. DNA samples were extracted and hybridized with the Affymetrix SNP 6.0 arrays using Human Mapping SNP6.0 assay kit following the manufacturer's standard protocol. The data were analyzed by two professional software packages, GCOS and Genotyping Console.</p><p><b>RESULTS</b>By using array-CGH technique, all the four cases were diagnosed precisely through identifying two duplications and two complex derivative chromosomes.</p><p><b>CONCLUSION</b>Array-CGH is an effective method for whole-genome identification of unbalanced chromosomal aberrations with high sensitivity and specificity. It has a great value to investigate the correlations between genotype and phenotype in clinical service, especially in prenatal diagnosis.</p>