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.

Parental origin of prenatally diagnosed pathogenic copy number variation in 56 pedigrees / 中华围产医学杂志

Objective:To investigate the prenatal management for pathogenic copy number variation (CNV) by analyzing the parental origin of CNV and pregnancy outcomes in 56 pedigrees.Methods:This study retrospectively analyzed the information of patients who received interventional prenatal diagnosis and chromosomal microarray analysis (CMA) at Guangzhou Women and Children's Medical Center from January 2015 to December 2020. The cases with pathogenic CNV indicated by CMA and receiving parental CMA for further verification were finally enrolled. Clinical data including prenatal diagnostic indications, chromosomal distribution of the pathogenic fragments and fragment sizes were collected and analyzed using t test. All cases were followed up by telephone and record review. Results:Fifty-six cases were included in this study. Pathogenic CNV in 13 (23.2%, 13/56) fetuses were inherited from one parent (eight from mothers and five from fathers), and mainly located in chromosomes 22 (3/13), 17 (3/11), 16 (2/7), 1 (2/4), and X (3/6) with fragment sizes all less than 3 Mb. The fragment size of inherited pathogenic CNV was significantly smaller than that of de novo CNV [1.69 (1.36-2.22) vs 7.54 (2.11-12.30) Mb, t=3.47, P=0.001]. Among the 43 cases with de novo pathogenic CNV, seven (16.3%) were lost to follow up and 35 (97.2%) terminated the pregnancy. The other one with a 0.58 Mb microruplication at 16p11.2 indicated at 37 gestational weeks gave birth to a baby weighting 2 900 g at 39 gestational weeks and no abnormalities were reported during an eight-month telephone follow-up. Two out of the 13 cases with inherited pathogenic CNV were lost to follow up and six pregnancies were terminated. The other five pregnancies were continued and babies were delivered with no abnormalities during a median follow-up period of 13 (4-15) months. Conclusion:Pathogenic CNV alone should not be the indication for pregnancy termination.

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.

Prenatal diagnosis and clinical outcomes of 297 fetuses with conotruncal defects / 中华妇产科杂志

Objective:To analyze the prenatal diagnosis results and pregnancy outcomes of conotruncal defects (CTD) fetuses, and to explore the correlation between the CTD and chromosome diseases.Methods:A total of 297 cases of invasive prenatal diagnosis and chromosome analysis were collected at the Prenatal Diagnosis Center of Guangzhou Women and Children′s Medical Center due to CTD from January 1st, 2011 to December 31th, 2019. According to ultrasonic diagnosis, CTD fetuses were divided into 6 subtypes: tetralogy of Fallot (109 cases), pulmonary atresia (30 cases), transposition of the great arteries (77 cases), double outlet right ventricle (53 cases), truncus arteriosus (14 cases) and interrupted aortic arch (14 cases). According to whether they were combined with intracardiac or extracardiac abnormalities, they were divided into simple group (134 cases), combined with other intracardiac abnormalities group (86 cases), combined with extracardiac abnormalities group (20 cases), combined with intracardiac and extracardiac abnormalities group (37 cases) and only combined with ultrasound soft marker group (20 cases), the last 4 groups were referred as non-simple types. The chromosome test results and pregnancy outcomes of each type and group were analyzed retrospectively.Results:Among the 297 CTD fetuses, the chromosome abnormality rate was 17.5% (52/297). There were 21 cases of abnormal chromosome number, 28 cases of pathogenetic copy number variantions and 3 cases of mosaics. All the 19 cases of micropathogenic fragments smaller than 5 Mb were detected by chromosomal microarray analysis (CMA). Among all the subtypes of CTD, the chromosomal abnormality rate of truncus arteriosus was the highest, at 7/14; while the rate of transposition of the great arteries was the lowest, at 5.2% (4/77). There were significant differences in the rate of chromosomal abnormalities between simple and non-simple types [10.4% (14/134) vs 23.3% (38/163); χ2 =8.428, P=0.004]. In each group, the chromosomal abnormality rate was the highest in the combined with intracardiac and extracardiac abnormalities group, at 37.8% (14/37), and the lowest in the simple group, at 10.4% (14/134). There was no significant difference in the rate of chromosomal abnormalities in all subtypes of simple group (all P>0.05). Among 112 cases of live birth, 1 case was 22q11.2 microdeletion syndrome, 5 cases of postnatal clinical diagnosis and prenatal ultrasound diagnosis were not completely consistent, 5 cases died after birth. Conclusions:The incidence of chromosomal abnormalities is high in fetuses with CTD. CTD fetuses with concurrent extrapardiac malformations are more likely to incorporate chromosomal abnormalities. CMA technology could be used as a first-line genetic detection method for CTD. After excluding chromosomal abnormalities, most of the children with CTD have good prognosis.

Genetic analysis and prenatal diagnosis of a fetus with Xq25 microduplication / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with structural brain abnormalities.@*METHODS@#The karyotypes of the fetus and its parents were analyzed by conventional G-banding. Chromosome microarray analysis (CMA) was carried out to detect chromosomal microdeletion and microduplication.@*RESULTS@#No kartotypic abnormality was detected in the fetus and its parents. CMA has identified a 194 kb microduplication at Xq25 in the fetus, which encompassed exons 4-35 of the STAG2 gene and was derived from its mother.@*CONCLUSION@#The Xq25 duplication encompassing part of the STAG2 gene probably underlay the brain malformation in the fetus.

A qualitative research on symptom experience in patients with acute coronary syndrome before diagnosis / 中国实用护理杂志

Objective:To explore the symptom experience of patients with acute coronary syndrome before diagnosis, in order to improve their early recognition ability, timely medical treatment rate and formulate relevant measures to provide reference.Methods:Semi-structured interview was performed in 18 patients with acute coronary syndrome from August 12 2020 to September 8 in Shanxi Provincial people′s Hospital using phenomenological research, and the data were analyzed under the guidance of symptom experience model.Results:A total of four themes were summarized: symptom perception: diseases being easily predicted, symptom experiences being diverse and diseases being easily overlooked; symptom evaluation: correct evaluation and evaluation bias; symptom response: self-response and family-society support; reflection on the process of symptom experience:medical behaviour and lack of awareness of disease.Conclusions:At present, the identification of acutecoronary syndrome is still a challenge. Patients should enrich relevant knowledge, pay attention to their own symptom experience, make the correct evaluation and deal with it effectively. Medical workers should carry out relevant education to improve the ability of patients to identify diseases.

Analysis of families with fetal congenital abnormalities but negative prenatal diagnosis by whole exome sequencing / 中华妇产科杂志

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

Application of whole exome sequencing technology in fetuses with congenital structural abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities.@*METHODS@#The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups.@*RESULTS@#A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history.@*CONCLUSION@#For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.

Application of chromosomal microarray analysis in 815 fetuses with increased nuchal translucency during early pregnancy / 中华医学遗传学杂志

OBJECTIVE@#To explore genetic etiology and prognosis for fetuses with increased nuchal translucency (NT).@*METHODS@#A total of 815 fetuses with increased NT (≥ 3.0 mm) were included. The fetuses were grouped by NT thickness and divided into 3.0-3.4 mm, 3.5-4.4 mm, 4.5-5.4 mm, 5.5- 6.4 mm and ≥ 6.5 mm groups. Based on the presence of additional abnormalities, the samples were divided into increased NT alone group and increased NT and other anomalies group. Chromosomal microarray analysis (CMA) was applied as a first-line test to detect pathogenic copy number variations (CNVs). The outcome of the pregnancies was followed up.@*RESULTS@#One hundred seventy-eight (21.8%) fetuses were found to harbor pathogenic CNVs, which included 138 (77.5%) with chromosomal aneuploidies, 14 (7.9%) with microdeletion/microduplication syndromes, and 26 (14.6%) harboring non-syndromic pathogenic CNVs. A significant difference was found in the detection rate of pathogenic CNVs between groups with different NT thickness. The detection rate of pathogenic CNVs also significantly differed between groups with regard to other structural abnormalities or the overall adverse pregnancy outcome.@*CONCLUSION@#CMA can be used as a first-line test for fetuses with increased NT during early pregnancy, with the overall detection rate of pathogenic CNVs being as high as 21.8%. Our results confirmed that NT thickness is correlated with other structural abnormalities and adverse pregnancy outcome, especially for those with NT ≥ 4.5 mm. At the same time, fetuses with other structural abnormalities are at an increased risk for adverse pregnancy outcome.

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.

The real experience of patients with enteral nutrition after gastro/jejunostomy and their caregivers: a qualitative research Meta-synthesis / 中国实用护理杂志

Objective:To systematically evaluate the qualitative study of the real experience of patients with enteral nutrition after gastro/jejunostomy and their caregivers and to deeply understand the real feelings and physical and mental experience of patients and caregivers.Methods:Databases were searched including PubMed, Embase, CINAHL, The Cochrane Library, Web of Science, PsycINFO, CNKI, Wanfang Database, VIP Database and CBM from inception to September 30th, 2019. To collect the qualitative studies on the real experience of patients with enteral nutrition after gastro/jejunostomy and their caregivers. According to the inclusion and exclusion criteria, the included literature was determined, the literature was evaluated according to the quality evaluation criteria of qualitative research of the JBI Evidence-based Health Care Center, and the results were integrated using a collective integration method.Results:A total of 11 studies were included and 37 results were extracted. Based on the quality of life theory, the topics extracted are as follows: patients with enteral nutrition after gastro/jejunostomy and their caregivers experienced dynamic cycle of change and challenge, coping and adaptation, demand and support in the domain of health and function, psychology/spiritual, socioeconomic and family.Conclusions:The four domains of quality of life of patients and caregivers were affected during enteral nutrition after gastro/jejunostomy. In particular, patients and caregivers showed strong inner and information needs in the psychological/spiritual and socioeconomic domain. It is suggested that medical staff should provide effective psychological, emotional and information support in disease treatment and nursing, in order to improve the quality of life of patients and caregivers.

De Novo and Inherited SETD1A Variants in Early-onset Epilepsy / 神经科学通报·英文版

Early-onset epilepsy is a neurological abnormality in childhood, and it is especially common in the first 2 years after birth. Seizures in early life mostly result from structural or metabolic disorders in the brain, and the genetic causes of idiopathic seizures have been extensively investigated. In this study, we identified four missense mutations in the SETD1A gene (SET domain-containing 1A, histone lysine methyltransferase): three de novo mutations in three individuals and one inherited mutation in a four-generation family. Whole-exome sequencing indicated that all four of these mutations were responsible for the seizures. Mutations of SETD1A have been implicated in schizophrenia and developmental disorders, so we examined the role of the four mutations (R913C, Q269R, G1369R, and R1392H) in neural development. We found that their expression in mouse primary cortical neurons affected excitatory synapse development. Moreover, expression of the R913C mutation also affected the migration of cortical neurons in the mouse brain. We further identified two common genes (Neurl4 and Usp39) affected by mutations of SETD1A. These results suggested that the mutations of SETD1A play a fundamental role in abnormal synaptic function and the development of neurons, so they may be pathogenic factors for neurodevelopmental disorders.

Analysis of 26 fetuses with congenital anomalies of the kidney and urinary tract by whole exome sequencing / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) by whole exome sequencing (WES).@*METHODS@#WES was performed on DNA extracted from cord blood samples of 26 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 19 cases, sequencing was performed on fetal DNA only, and the turnaround time was 11-12 weeks. For the remaining 7 cases, the fetus and its parents were sequenced simultaneously, and the turnaround time was 8-9 weeks.@*RESULTS@#Of the 26 cases, pathogenic variants were identified in 4 (15.4%) cases, which respectively involved UMOD, NEK8, HNF1B, and BBS2 genes, and likely pathogenic variants were identified in 2 (7.7%) cases, which respectively involved HSPD1 and GRIN2B genes. Two of the 4 cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/19 (10.5%) for isolated CAKUT and 4/7 (57.1%) for CAKUT with additional anomalies.@*CONCLUSION@#The application of WES as a prenatal diagnostic approach for CAKUT fetuses with or without other anomalies allowed early and accurate diagnosis and improved their clinical management.

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 chromosome microarray analysis in 489 children with developmental delay/intellectual disability / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of chromosome microarray analysis (CMA) for identifying the etiology of developmental delay/intellectual disability (DD/ID).</p><p><b>METHODS</b>A total of 489 children referred for DD/ID with or without other abnormalities were recruited. All patients showed a normal karyotype. DNA was extracted and hybridized with Affymetrix CytoScan 750K array by following the manufacturer's protocol. The data was analyzed with CHAS v2.0 software.</p><p><b>RESULTS</b>The children were classified as with isolated DD/ID (n=358), DD/ID with epilepsy (n=49), and DD/ID with other structural anomalies (n=82). Pathogenic copy number variants (CNVs) were identified in 126 cases (25.8%), which included 89 (24.9%, 89/358) of whose with isolated DD/ID, 13 (26.5%, 13/49) of those with DD/ID and epilepsy, and 24 (29.3%, 24/82) of whose with DD/ID and other structural anomalies [P=0.064 (24.9% vs. 26.5%), P=0.679 (24.9% vs. 29.3%), and P=0.113 (26.5% vs. 29.3%), respectively]. Among the 126 cases, 79 were identified as microdeletion/microduplication syndromes, which included 15q24 microdeletion syndrome, Xq28 microduplication syndrome, and Lowe syndrome. Forty-seven cases had de novo pathogenic CNVs. ABAT, PMM2, FTSJ1, DYNC1H1 and SETBP1 were considered as candidate genes for DD/ID.</p><p><b>CONCLUSION</b>CMA is an effective method for identifying the etiology of DD/ID and is capable of identifying microdeletion/microduplication syndromes as well as de novo pathogenic CNVs which may be missed by conventional karyotyping. Based on the results, candidate genes for DD/ID may be identified.</p>

Relationship between absent or hypoplastic fetal nasal bone and chromosome abnormalities: analysis of 187 cases / 中华围产医学杂志

Objective To investigate the relationship between absent or hypoplastic fetal nasal bone and chromosome abnormalities.Methods From January 2010 to April 2014,187 fetuses were found to have absent or hypoplastic nasal bone by prenatal ultrasound scanning in Guangzhou Maternal and Children's Hospital.All the pregnant women should undergo interventional prenatal diagnosis for fetal chromosome abnormalities,and should be followed up for three months after the expected delivery date.The correlation between absent or hypoplastic fetal nasal bone and chromosome abnormalities,and the effects of complicating structural defects were analyzed by descriptive analysis and the Chi-square test.Results Of the 187 pregnant women,126 underwent interventional prenatal diagnostic tests,and fetal chromosome abnormalities were detected in 36 cases (28.6％),including 26 cases (20.6％) of trisomy 21,6 cases (4.8％) of trisomy 18,three cases (2.4％) of trisomy 13 and one sex chromosome chimerism.In the 126 cases received prenatal diagnosis,the incidence of chromosome abnormalities in fetuses without other structural defects was significantly lower than that with structural defects [12.7％ (8/63) vs 44.4％ (28/63),x2=15.556,P=0.000].Among 63 cases without other structural defects,seven fetuses were confirmed to have chromosome abnormalities in 14 women with high risk by Down syndrome screening,no chromosome abnormalities were found in 39 pregnant women with low risk by Down syndrome screening,and one sex chromosome chimerism was found in the other ten women who did not undergo Down syndrome screening.Absent or hypoplastic nasal bone detected in the first trimester resulted in a higher risk of chromosome abnormalities than that detected in the second and the third trimester [25.5％ (28/110) vs 10.4％ (8/77),x2=6.613,P=0.007].Conclusions When a fetus is found to have absent or hypoplastic nasal bone,it is necessary to perform Down syndrome screening and a detailed morphology scan.Women shown to have fetuses with absent or hypoplastic nasal bone with other structural defects or high risk by Down syndrome screening should undergo prenatal diagnostic tests to exclude fetal chromosome abnormalities.

The prenatal ultrasound and magnatic resonance imaging characteristics of fetal intracranial hemorrhage / 中华医学超声杂志（电子版）

Objective To investigate the diagnostic value of prenatal ultrasonography and magnatic resonance imaging in the fetal intracranial hemorrhage. Methods The 20 antenatal diagnosed ICH cases was collected from 31 200 prenatal diagnosis units in Guangzhou Women and Children′s Medical Center from July 2012 to June 2014. Maternal characteristics, ultrasound, and magnetic resonance imaging findings, clinical course, and postnatal outcome were reviewed. Results Twenty consecutive cases of fetal ICH were evaluated. All cases were diagnosed at mid or third trimester. Transabdominal ultrasound showed 9 cases of hyper echoic lesions in the lateral ventricle, 2 cases of hypoechonic lesions, 2 cases of irregular mixed echo in the parenchyma, 1 case of hyperechoic cerebellar hemisphere with infarction, and 1 case of abnormal choroid plexus. Seventeen cases were associated with ventriculomegaly, brain compression or brain midline displacement. MRI showed the nodular, patchy or linear low signal on T2WI and high signal on T1WI. Some cases were combined with cortex lesions or abnormal parenchyma. ICH was complicated with other structural abnormalities:1 case of cleft palate, 2 cases of spinal deformity and 3 cases of other cerebral cortical malformations. Prenatal diagnosis results were:2 cases diagnosed as positive cytomegalovirus infection and no chromosome abnormalities found in all cases. The follow up results were:1 case was lost, 16 cases were terminated after prenatal diagnosis. Among the 3 survival cases, 1 case has the neurological complication and the other two were normal till now. Conclusions Fetal intracranial hemorrhage has some image features on ultrasound and magnetic resonance. Ultrasound showed hyper echoic lesions with ventriculomegaly. MRI showed the nodular, patchy or linear low signal on T2WI and high signal on T1WI. MRI may contribute to the accuracy of diagnosis, particularly in bleeding site. The regular ultrasonic monitoring is helpful to improve the detection rate.

Application of whole-genome and high-resolution chromosome microarray analysis for the investigation of fetuses with ultrasound abnormalities / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of whole-genome high-resolution chromosome microarray analysis (CMA) for the investigation of fetuses with ultrasound abnormalities.</p><p><b>METHODS</b>Whole genome high-resolution CytoScanHD array from Affymetrix was employed to investigate 651 fetuses with structural abnormalities detected by ultrasound, for whom standard G-banded chromosome analysis has revealed a normal karyotype. The fetuses were divided into a single malformation group (n=264) and a multiple malformations group (n=387). In total there were 130 chorionic villus samples, 192 amniotic fluid samples and 329 cord blood samples. Extraction of fetal DNA and CMA experiment have followed the standard guidelines from the manufacturers. All copy number variations (CNVs) detected by CMA were confirmed by fluorescence in situ hybridization (FISH) or real-time polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>CMA analysis has detected genomic CNVs in 475 (73%) cases. Clinically significant CNVs were found in 11.5% (75/651) of fetuses, including two uniparental disomies (UPD) and two cryptic mosaicisms. Variations of unknown significance (VOUS) was found in 2.0% (13/651) of tested fetuses.</p><p><b>CONCLUSION</b>Above results have suggested that whole-genome and high-resolution CMA is valuable for the analysis of fetuses with structural abnormalities detected by ultrasound, which can increase the detection rate by approximately 11%. CMA using single nucleotide polymorphism (SNP) array has the ability to detect UPD and low-level mosaicisms. Sufficient communication between technicians and genetic counselors, parental testing and comparison the results with in-house and relevant online databases can significantly reduce the rate of VOUS.</p>

Results of prenatal screening for fetal chromosome abnormality during the first trimester pregnancy in Guangzhou / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the efficiency of first trimester prenatal screening for fetal chromosome abnormality using maternal serum marker test and(or) plus nuchal translucency (NT) in Guangzhou region.</p><p><b>METHODS</b>The results of prenatal screening were retrospectively analyzed among 43 703 women with singleton pregnancies from January 2007 to September 2012. A total of 43 703 pregnancies between 9 and 13(+6) weeks of pregnancy were collected and analyzed for maternal serum pregnancy-associated plasma protein A (PAPPA), free β -human chorionic gonadotropin (free β -hCG) with or without crown-rump length (CRL). Nuchal translucency was measured by ultrasonographic scan between 11 and 13(+6) weeks of pregnancy. Gestational age was estimated by ultrasonographic scan. The risk values of Down syndrome (DS) and trisomy 18 were calculated using the software Lifcycle. Comparing the difference between the combined screening (PAPPA, free β -hCG and NT) and serum marker screening (PAPPA and free β -hCG).</p><p><b>RESULTS</b>Among the 43 703 pregnant women, screening showed that 1385 (3.17%) were Down syndrome positive and 55 (0.13%) were trisomy 18 positive. The final outcomes of pregnancy showed that 142 cases presented chromosomal abnormalities, of which 54 cases suffered from Down syndrome, 13 had trisomy 18, and 75 had other chromosome abnormalities. The total detection rate of Down syndrome and trisomy 18 were 83.33% and 76.92%, respectively.The positive rate is lower, and the detection rate is higher in combined screening group than serum marker screening group. The median PAPPA MoM was lower and the median free β -hCG MoM and NT measured value was higher in Down syndrome pregnancies than control group. The median PAPPA and free β -hCG MoM were lower and the median NT measured value was higher in trisomy 18 pregnancies than control group.</p><p><b>CONCLUSION</b>The first trimester prenatal screening can effectively detect Down syndrome and trisomy 18 pregnancy. The combined screening method is superior to the serum marker screening and is the preferred strategy in the first trimester prenatal screening.</p>

Prenatal ultrasound screening for fetal cleft lip and palate and related abnormalities / 中华围产医学杂志

Objective To evaluate the sensitivity and specificity of prenatal ultrasound for detecting fetal cleft lip and palate,and the diagnosis rate of associated congenital structural and chromosomal abnormalities.Methods Thirty one thousand two hundred and forty five singleton pregnant women accepted prenatal examination and delivered in Guangzhou Women & Children' s Medical Center from Jan.2006 to Dec.2010 were recruited in this study.All pregnant women underwent prenatal ultrasound screening during second trimester,and whose fetuses were suspected to be cleft lip and palate were suggested to accept karyotype analysis.All babies delivered received oral examination to diagnose cleft lip and palate.Results Cleft lip and palate was diagnosed in 48 cases (1.5‰,48/31 245).Among which,there were 16 cases (33.3％,16/48) of cleft lip,21 cases (43.8％,21/48) of cleft lip with cleft palate and 11 cases (22.9％,11/48) of cleft palate.Prenatal ultrasound screening suggested 18 cases of cleft lip and 14 cases were comfirmed after birth with the accuracy rate of 77.8％,3 cases were diagnosed to be cleft lip with cleft palate and one cases was misdiagnosed.Prenatal ultrasound screening suggested 18 cases of cleft lip with cleft palate in accordance with the diagnosis after birth.Thirteen cases were normal in prenatal ultrasound screening,but two were diagnosed as cleft lip and 11 were diagnosed as cleft palate after birth.The sensitivity of prenatal ultrasound screening for cleft lip and cleft lip with cleft palate was 86.5％(32/37),and the sensitivity for cleft lip and palate was 66.7％ (32/48),the false positive rate was 2.1％ (1/48).Ten cases (27.8％,10/36) of cleft lip with cleft palate were found to be complicated with other abnormalities.Nine of the 18 cases prenatally diagnosed cleft lip with cleft palate accepted karyotype analysis and 7 were abnormal.Twenty-three of 36 cases with fetal cleft lip and palate in prenatal ultrasound screening were induced.Conclusions Ultrasound screening has a high sensitivity for detection of cleft lip with or without cleft palate,but difficult to detect cleft palate.The risk of combining with chromosomal defects in cleft lip fetus is very low,but might increase once associated with cleft palate.