Indications for prenatal diagnosis and pregnancy outcomes of Turner syndrome with different karyotypes in 205 cases / 中华围产医学杂志

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.

Prenatal diagnosis and pregnancy outcome of increased nuchal translucency with or without nuchal cystic hygroma in fetuses during first trimester / 中华围产医学杂志

Objective:To compare the prenatal diagnosis and pregnancy outcome of increased nuchal translucency (NT) with or without nuchal cystic hygroma (CH) in fetuses with first-trimester NT ≥5 mm.Methods:Data from 131 fetuses with NT ≥5 mm who received invasive prenatal diagnosis at Guangzhou Women and Children's Medical Center from July 2017 to December 2020 were retrospectively collected and analyzed. Those with a septum in the cyst were grouped as NT with CH group ( n=57), and those without as increased NT without CH group ( n=74). Genetic test results, incidence of structural malformations, survival rate after birth were compared using Chi-square test or Fisher's exact test and non-parametric test. Results:There was no significant difference in the incidence of fetal genetic abnormalities[67.6%(50/74) vs 61.4%(35/57), χ 2=0.54, P=0.464], ultrasonic structural malformations [21.6%(16/74) vs 33.3%(19/57), χ 2=2.26, P=0.133], or in the survival rate (12/14 vs 3/8, P=0.053) between increased NT without CH group and NT with CH group. Conclusions:For increased NT with or without CH, although the two groups had different spectrum of disease, they had a high incidence of chromosomal abnormalities and structural malformations, and both groups had a certain healthy survival rate after birth.

Research progress of CCL20-CCR6 axis and epithelial-mesenchymal transition in breast cancer / 国际外科学杂志

CCL20 and CCR6 are chemokines produced by a variety of cells. CCL20 and CCR6 combine to stimulate a series of downstream pathways, participate in the occurrence and development of various malignant tumors, and also play an important role in the invasion and metastasis of breast cancer and the process of chemotherapy resistance. Epithelial-mesenchymal transformation (EMT) is a key step in the process of tumor cell metastasis, which is characterized by loss of cell adhesion, down-regulation of E-cherherin expression, up-regulation of mesenchymal markers and fibrinectin expression, and enhancement of cell motor ability and invasion ability. This article reviews the research of CCL20-CCR6 biological axis and EMT on invasion and metastasis of breast cancer cells.

Consistency between quantitative fluorescent-polymerase chain reaction and karyotyping in prenatal diagnosis / 中华围产医学杂志

Objective:To analyze the consistency between karyotyping and quantitative fluorescent- polymerase chain reaction (QF-PCR) in prenatal diagnosis.Methods:This study retrospectively analyzed the clinical data of 10 967 patients undergoing karyotyping and QF-PCR for prenatal diagnosis in Guangzhou Women and Children's Hospital from January 2010 to December 2017. The failure rate, results, and diagnosis of common chromosomal disorders of the two methods were compared. The sensitivity and specificity of QF-PCR in detecting chromosomal mosaicism were evaluated using the receiver operative characteristic (ROC) curve.Results:(1) The failure rates of karyotyping and QF-PCR were 0.99% (109/10 967) and 0.10% (11/10 967), respectively. (2) The karyotypes of 9 960 out of the 10 858 successfully cultured samples were normal, and 99.89% (9 949/9 960) results were consistent between the two methods. The other 898 cases included 694 (77.28%) with common chromosomal abnormalities (trisomy 21, 18 and 13 and sex chromosomal abnormality) and 204 (22.72%) with other chromosomal abnormalities. The consistency between the two methods in detecting common chromosomal abnormalities was 95.68% (664/694). (3) The consistency in the detection of trisomy 21, 18 and 13 and sex chromosomal abnormality between karyotyping and QF-PCR were 99.74% (382/383), 100.00% (125/125), 100.00% (33/33) and 81.05% (124/153). However, the common chromosomal mosaicism was only noted for 44.44% (24/54). (4) Among cases with a mosaic ratio over 18.5%, the sensitivity and specificity of QF-PCR were 0.958 (95% CI: 0.789-0.999) and 0.600 (95% CI: 0.406-0.773) with the area under the ROC curve (AUC) of 0.811 (95% CI: 0.696-0.926, P<0.001). (5) Thirty cases with negative QF-PCR results but positive mosaic chromosomal aberrations were followed up. Ten (33.3%) pregnant women terminated their pregnancies, and two (6.7%) were lost to follow-up. The other 18 cases delivered healthy neonates that all survived after birth. Conclusions:In prenatal diagnosis, QF-PCR and karyotyping were highly consistent in the detection of trisomy 21, 13, and 18, but have significant discordance in the diagnosis of sex chromosomal abnormality.

Chorionic villus cell culture and karyotype analysis in 1983 cases of spontaneous miscarriage / 中华妇产科杂志

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.

Application of array-based comparative genomic hybridization in precise diagnosis of unbalanced chromosome aberration / 中华医学遗传学杂志

<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>

Application of spectral karyotyping in diagnosis and prenatal diagnosis of the marker chromosome / 中华妇产科杂志

Objective To determine the value of spectral karyotyping(SKY)in identification of the marker chromosome.Methods Selected six cases that could not be identified in clinic were studied,using samples of peripheral blood from four cases,and samples of amonic fluid and fetal cord blood for prenatal diagnosis in two cases were investigated.All cases were analyzed with the routine SKY method.and the results with the SKY View software.The SKY results were identified by using fluorescence in situ hybridization(FISH).And C-banding technique was used to help diagnose the heterochromatin.Results SKY wag successfully performed on all of 6 cases.The origin of all marker chromosomes was identified by SKY.Except case No.4,the others were confirmed by FISH.It helped determine the pregnancy outcome in two cases of prenatal diagnosis:one case of genetic marker chromosome continued the pregnancy,and another case of de novo marker chromosome was terminated of the pregnancy.Conclusion SKY may be a vahable tool to diagnose the marker chromosome with rapidness,direct-viewing and sensitiveness.It can be used to assess the prognosis and the pregnancy outcome.