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Objectives: The phenotypes of Xp22.33 or Yp11.32 microdeletions comprising the short-stature homeobox ( SHOX ) gene have been extensively described in adults and children. Herein, the prenatal ultrasound phenotype and pregnancy outcomes of fetuses with Xp22.33/Yp11.32 microdeletions were analyzed to improve our understanding, diagnosis, and monitoring of this genetic condition in the fetal stage., Methods: A total of 9,100 pregnant women referred to tertiary units for prenatal diagnosis were evaluated by chromosomal microarray analysis(CMA)., Results: Seven (0.08 %) fetuses had Xp22.33/Yp11.32 microdeletions, ranging from 243 kb to 1.1 Mb, that comprised SHOX . The ultrasonic phenotypes differed among these fetuses, with three fetuses presenting abnormal bone development, one had labial-palatal deformity and strawberry head, two had an abnormal ultrasonic soft marker, and one had no abnormalities. After genetic counseling, only one couple underwent pedigree assessment, which confirmed the paternal origin of the microdeletion. This infant presented delayed speech development, whereas other three infants showed a typical postnatal development. In three cases, the parents chose to terminate the pregnancy., Conclusions: The ultrasonic phenotype of fetuses with Xp22.33/Yp11.32 microdeletions resulting in SHOX heterozygosity loss is variable. Prenatal CMA can quickly and effectively diagnose Xp22.33/Yp11.32 microdeletions and SHOX loss, which may help prenatal counseling., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Although non-invasive prenatal testing (NIPT) is widely used to detect fetal abnormalities, the results of NIPT vary by population, and data for the screening efficiency of NIPT positive predictive value (PPV) from different populations is limited. Herein, we retrospectively analyzed the NIPT results in a large multicenter study involving 52,855 pregnant women. Depending on gestational age, amniotic fluid or umbilical cord blood was extracted for karyotype and/or chromosome microarray analysis (CMA) in NIPT-positive patients, and the PPV and follow-up data were evaluated to determine its clinical value. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 chromosomal abnormalities, with a PPV of 45.1%. PPV for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosomal aneuploidies (SCAs), and copy number variations (CNVs) were 78.9, 35.3, 22.2, 36.9, and 32.9%, respectively. The PPVs for T21, T18, and T13 increased with age, whereas the PPVs for SCAs and CNVs had little correlation with age. The PPV was significantly higher in patients with advanced age and abnormal ultrasound. The NIPT results are affected by population characteristics. NIPT had a high PPV for T21 and a low PPV for T13 and T18, and screening for SCAs and CNVs showed clinical significance in southern China.

Objectives: The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years., Methods: We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded., Results: Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012-2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017-2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis., Conclusions: Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Multicystic dysplastic kidney (MCDK) is one of the most common fetal malformations, but its etiology remains unclear. Identification of the molecular etiology could provide a basis for prenatal diagnosis, consultation, and prognosis evaluation for MCDK fetuses. We used chromosome microarray analysis (CMA) and whole-exome sequencing (WES) to conduct genetic tests on MCDK fetuses and explore their genetic etiology. A total of 108 MCDK fetuses with or without other extrarenal abnormalities were selected. Karyotype analysis of 108 MCDK fetuses showed an abnormal karyotype in 4 (3.7%, 4/108) of the fetuses. However, CMA detected 15 abnormal copy number variations (CNVs) (14 pathogenic CNVs, and one variant of unknown significance [VUS] CNVs), in addition to four cases that were consistent with the results of karyotype analysis. Out of the 14 pathogenic CNVs cases, three were of 17q12 microdeletion, two of 22q11.21 microdeletion, 22q11.21 microduplication uniparental disomy (UPD), and one case of 4q31.3q32.2 microdeletion, 7q11.23 microduplication, 15q11.2 microdeletion, 16p11.2 microdeletion, and 17p12 microdeletion. Of the 89 MCDK fetuses with normal karyotype analysis and CMA, 15 were tested by WES. Two (13.3%, 2/15) fetuses were identified by WES as Bardet-Biedl syndrome (BBS) 1 and BBS2. Combined application of CMA-WES to detect MCDK fetuses can significantly improve the detection rate of genetic etiology, providing a basis for consultation, and prognosis evaluation.

Objective: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS)., Methods: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019., Results: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation., Conclusion: Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.

The q11.2 region on chromosome 22 contains numerous low-copy repeats that lead to deleted or duplicated regions in the chromosome, thereby resulting in different syndromes characterized by intellectual disabilities or congenital anomalies. The association between patient phenotypes and 22q11.2 copy number abnormalities has been previously described in postnatal cases; however, these features have not been systematically evaluated in prenatal cases because of limitations in phenotypic identification in prenatal testing. In this study, we investigated the detection rate of 22q11.2 copy number abnormalities in 2500 fetuses using single nucleotide polymorphism (SNP) array and determined the common abnormal ultrasound findings in fetuses carrying the 22q11.2 copy number abnormalities. The 22q11.2 copy number abnormalities were identified in 13 fetuses with cardiovascular malformations (6/13), kidney malformations (3/13), isolated ultrasound markers (3/13), or high-risk Down syndrome based on maternal serum screening (1/13). Approximately 0.5% (13/2500) of the fetuses harbored 22q11.2 copy number abnormalities. The most frequent ultrasound findings in fetuses with these abnormalities were cardiovascular malformations, followed by kidney malformations and isolated ultrasound markers. Prenatal diagnosis of these genetic abnormalities allows for the delineation of differential diagnoses, characterization of a wide spectrum of associated malformations, and determination of associations that exist between prenatal diagnosis and obstetrical outcomes.

Because the numbers of detected fetal abnormalities increase as gestation progresses, we evaluated the safety and efficacy of cordocentesis for single nucleotide polymorphism (SNP) analysis tests in 754 women during third trimester pregnancy. Conventional karyotyping was performed on all fetuses, and Affymetrix CytoScan HD was used for SNP-array testing. In addition to the 24 cases with chromosomal abnormalities detected with conventional karyotyping analysis, the SNP-array test identified 56 (7.4%) cases with normal karyotypes but abnormal copy number variations (CNVs). Of those, 24 were pathogenic CNVs and 32 were of uncertain clinical significance. In 742 of the cases, there were abnormal sonographic findings, and cytogenetic abnormalities were detected in 76 cases (10.2%). The largest number of abnormalities involved multiple malformations (21.7%), followed by defects in the lymphatics or effusion (19.0%) or urogenital system (15.3%). The use of SNP-array test fully complemented chromosome karyotype analysis after late cordocentesis. It also improved the detection rate for fetal chromosomal abnormalities and was effective for preventing and controlling the occurrence of birth defects.

Background: Submicroscopic chromosomal imbalance is associated with an increased nuchal translucency (NT). Most previous research has recommended the use of chromosomal microarray analysis (CMA) for prenatal diagnosis if the NT ≥ 3.5 mm. However, there is no current global consensus on the cutoff value for CMA. In this study, we aimed to discuss the fetuses with smaller increased NT which was between cutoff value of NT for karyotype analysis (NT of 2.5 mm in China) and the recommended cutoff value for CMA (NT of 3.5 mm) whether should be excluded from CMA test., Methods: Singleton pregnant women (N = 192) who had undergone invasive procedures owing to an increased NT (NT ≥ 2.5 mm) were enrolled. Fetal cells were collected and subjected to single nucleotide polymorphism array and karyotype analyses simultaneously. Cases were excluded if the karyotype analysis indicated aneuploidy and apparent structural aberrations., Results: Fourteen cases of aneuploidy and four cases of structural abnormalities were excluded. Of the remaining 174 cases, 119 fetuses had NTs of 2.5-3.4 mm, and 55 fetuses with NT ≥ 3.5 mm. Eleven copy number variants (CNVs) were identified. In fetuses with smaller NTs, six (6/119, 5.9%) variations were detected, including two (2/119, 1.6%) clinically significant CNVs (pathogenic or likely pathogenic CNV), one  likely benign CNV, two variants unknown significance, and one incidental CNV. Five (5/55, 9.1%) variations were found in fetuses with NT ≥ 3.5 mm. Among these CNVs, three (3/55, 5.5%) cases had clinically significant CNVs, and two had likely benign CNV. There were no statistically significant differences in the incidence of all CNVs and clinically significant CNVs in the two groups (p > 0.05)., Conclusion: CMA improved the diagnostic yield of chromosomal aberrations for fetuses with NTs of 2.5-3.4 mm and apparently normal karyotype, regardless of whether other ultrasonic abnormalities were observed., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Objective: To determine the origin of supernumerary small marker chromosomes (sSMCs) carried by two fetuses., Methods: Single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis were carried out on cells cultured from the amniotic fluid samples., Results: SNP-array analysis showed both fetuses to be arr[hg19]22q11.1q11.21(16 888 899-18 649 190)×4, with a duplicated 1.7 Mb region (16 888 899-18 649 190) leading to partial tetrasomy of 22q11.1-22q11.21. FISH confirmed that both fetuses were 47,XN,+mar.ish idic(22)(q11.2) (RP11-958H20 ++),which suggested a diagnosis of Cat-eye syndrome (CES). The appearance of abortuses were consistent with the diagnosis of CES., Conclusion: Two fetuses with CES were diagnosed by genetic testing. The latter has provided a basis for genetic counseling.

Background: Congenital heart disease (CHD) is one of the most common birth defects; however, the mechanisms underlying its development are poorly understood. Recently, heritable genetic factors, including copy number variations (CNVs) and single nucleotide polymorphisms (SNPs), have been implicated in its etiology. The aim of this study was to investigate the utility of a SNP array for the prenatal diagnosis of CHD and the improvement of prenatal genetic counseling and to compare this approach to traditional chromosome analysis., Methods: One hundred and fortysix cases of CHD detected by prenatal echocardiography were analyzed. Of these, 110 were isolated CHD and 36 were of CHD with extracardiac defects. SNP analysis was performed using the Affymetrix CytoScan HD platform, which was followed by karyotype analysis. All annotated CNVs were validated by fluorescence in situ hybridization., Results: Karyotype analysis identified chromosomal abnormalities in 19 of 146 cases. In addition to the 15 chromosomal abnormalities that were consistent with the results of karyotype analysis, the SNP array identified abnormal CNVs in an additional 15.2% (22/145) cases; of these, 15 were pathogenic CNVs, three were variations of uncertain clinical significance, and four were benign CNVs. The rates at which the SNP array detected pathogenic CNVs differed significantly between cases of isolated CHD and CHD with extracardiac defects (13.6% vs. 72.2%, P = .001). The results of the SNP array also affected the rate of pregnancy termination., Conclusion: Combining SNP array with cytogenetic analyses is particularly effective for identifying chromosomal abnormalities in CNVs in fetuses with CHD, which also affects obstetrical outcomes.

The phenotypes of Xp22.33 or Yp11.32 microdeletions comprising the short-stature homeobox (SHOX) gene have been extensively described in adults and children. Herein, the prenatal ultrasound phenotype and pregnancy outcomes of fetuses with Xp22.33/Yp11.32 microdeletions were analyzed to improve our understanding, diagnosis, and monitoring of this genetic condition in the fetal stage. A total of 9,100 pregnant women referred to tertiary units for prenatal diagnosis were evaluated by chromosomal microarray analysis(CMA). Seven (0.08 %) fetuses had Xp22.33/Yp11.32 microdeletions, ranging from 243 kb to 1.1 Mb, that comprised SHOX. The ultrasonic phenotypes differed among these fetuses, with three fetuses presenting abnormal bone development, one had labial-palatal deformity and strawberry head, two had an abnormal ultrasonic soft marker, and one had no abnormalities. After genetic counseling, only one couple underwent pedigree assessment, which confirmed the paternal origin of the microdeletion. This infant presented delayed speech development, whereas other three infants showed a typical postnatal development. In three cases, the parents chose to terminate the pregnancy. The ultrasonic phenotype of fetuses with Xp22.33/Yp11.32 microdeletions resulting in SHOX heterozygosity loss is variable. Prenatal CMA can quickly and effectively diagnose Xp22.33/Yp11.32 microdeletions and SHOX loss, which may help prenatal counseling. [ABSTRACT FROM AUTHOR]

Background and Purpose: The application of classical cytogenetic and DNA‐based molecular techniques to detect cell lineages of mosaicism derived from cultured or noncultured fetal cells may result in discordant results. This retrospective study aimed to assess the inconsistent diagnostic outcomes, technical availability, and limitations of chromosomal microarray analysis (CMA) and karyotyping for mosaicism. Methodology: A total of 75 fetuses diagnosed with mosaicism by karyotype analysis or CMA were selected, and the results from both the methods were compared and further analyzed. Results: A total of 42 (56%, 42/75) CMA results were consistent with karyotypes, consisting of 22 cases of mosaic sex chromosomal abnormalities, 8 routine autosomal aneuploidy cases, 8 other autosome aneuploidy cases, 3 large cryptic genomic rearrangements, and 1 small supernumerary marker chromosome. Discrepancy between karyotype analysis and CMA was observed in 33 (44%, 33/75) mosaicisms involving 15 sex chromosomal abnormalities, 1 routine autosomal aneuploidies, 5 other autosome aneuploidy cases, 8 large cryptic genomic rearrangements, and 4 small supernumerary marker chromosomes. Conclusion: Considering the disparities between methods as well as the cell populations analyzed, both CMA and karyotype analysis have their own advantages and disadvantages. Therefore, CMA should ideally be used in combination with karyotyping to detect more cases of mosaicism than using either test alone. [ABSTRACT FROM AUTHOR]

Background: With the advancement of molecular technology, fetal talipes equinovarus (TE) is believed to be not only associated with chromosome aneuploidy, but also related to chromosomal microdeletion and microduplication. The study aimed to explore the molecular etiology of fetal TE and provide more information for the clinical screening and genetic counseling of TE by Chromosomal Microarray Analysis (CMA). Methods: This retrospectively study included 131 fetuses with TE identified by ultrasonography. Conventional karyotyping and SNP array analysis were performed for all the subjects. They were divided into isolated TE group (n = 55) and complex group (n = 76) according to structural anomalies. Results: Among the total of 131 fetuses, karyotype analysis found 12(9.2%) abnormal results, while SNP array found 27 (20.6%) cases. Trisomy 18 was detected most frequently among abnormal karyotypes. The detection rate of SNP array was significantly higher than that of traditional chromosome karyotype analysis (P < 0.05). SNP array detected 15 (11.5%) cases of submicroscopic abnormalities that karyotype analysis did not find. The most common CNV was the 22q11.2 microdeletion. For both analyses, the overall detection rates were significantly higher in the complex TE group than in the isolated TE group (karyotype: P < 0.05; SNP array: P < 0.05). The incremental yield of chromosomal abnormalities in fetuses with unilateral TE (22.0%) was higher than in fetuses with bilateral TE (19.8%), but this difference was not statistically significant (P > 0.05). Abnormal chromosomes were most frequently detected in fetuses with TE plus cardiovascular system abnormalities. Conclusion: Fetal TE is related to chromosomal microdeletion or microduplication. Prenatal diagnosis is recommended for fetuses with TE, and CMA testing is preferred. CMA can improve the detection rate of chromosomal abnormalities associated with fetal TE, especially in pregnancies with complex TE. [ABSTRACT FROM AUTHOR]

Background: The genetic etiology of congenital pulmonary stenosis (PS) in fetuses remains inadequately studied. We used karyotype analysis and chromosomal microarray analysis (CMA) to investigate the genetic aberrations associated with PS in human fetuses. Methods: A retrospective analysis was performed on 84 fetuses with congenital PS in southern China. Fetal amniotic fluid and umbilical cord blood samples were obtained for chromosomal karyotype analysis and CMA. Results: The rate of pathogenic copy number variation (CNV) was 15.5% (13/84) after karyotyping and CMA. An abnormal karyotype was detected in five cases (6.0%, 5/84) via karyotyping, whereas pathogenic CNVs were detected in 13 cases (15.5%, 13/84) via CMA. In addition to the five abnormal karyotypes detected using karyotype analysis, eight additional chromosomal microduplications and microdeletions were detected using CMA, comprising three cases of 22q11.21 microdeletion; two cases of 16p11.2 microdeletion; one case of simultaneous 18q23 microdeletion and 22q13.33 microduplication; one case of 15q24.1q24.2 microdeletion; and one case of 1q21.1q21.2 microduplication. The rate of pathogenic CNV occurrence was 11.5% in fetuses with isolated PS and 17.2% in fetuses with PS combined with other ultrasound abnormalities. This difference between the two experimental groups was statistically significant. Among 84 fetuses with PS, 39 pregnancies were terminated, and five were lost to follow-up. Conclusions: CMA was not only conducive to detect PS-related pathogenic genomic abnormalities but also to accurately evaluate fetal prognosis in genetic counseling. The early detection of PS and genomic abnormalities will exerta positive impact on fetal intervention and the related prognosis of PS in perinatal infants. [ABSTRACT FROM AUTHOR]

Numerous studies have evaluated the use of single nucleotide polymorphism array (SNP-array) in prenatal diagnostics, but very few have evaluated its application under different risk conditions. Here, SNP-array was used for the retrospective analysis of 8386 pregnancies and the cases were categorized into seven groups. Pathogenic copy number variations (pCNVs) were found in 699 (8.3%, 699/8386) cases. Among the seven different risk factor groups, the non-invasive prenatal testing-positive group had the highest pCNVs rate (35.3%), followed by the abnormal ultrasound structure group (12.8%), and then the chromosomal abnormalities in the couples group (9.5%). Notably the adverse pregnancy history group presented with the lowest pCNVs rate (2.8%). Further evaluation of the 1495 cases with ultrasound abnormalities revealed that the highest pCNV rates were recorded in those cases with multiple system structure abnormalities (22.6%), followed by the groups with skeletal system (11.6%) and urinary system abnormalities (11.2%). A total of 3424 fetuses with ultrasonic soft markers were classified as having one, two, or three ultrasonic soft markers. The different pCNV rates in the three groups were statistically significant. There was little correlation between pCNVs and a previous history of adverse pregnancy outcomes, suggesting that genetic screening under these conditions should be evaluated on a case-by-case basis. [ABSTRACT FROM AUTHOR]

Objectives: 16p13.11 microdeletion/microduplication are rare genetic diseases with incomplete penetrance, most of which have been reported in adults and children, with ultrasound phenotyping in fetuses rarely described. Here, we have analyzed prenatal ultrasound phenotypic characteristics associated with 16p13.11 microdeletion/microduplication, in order to improve the understanding, diagnosis and monitoring of this disease in the fetus. Methods: A total of 9000 pregnant women who underwent invasive prenatal diagnosis for karyotyping and SNP-array were retrospectively analyzed in tertiary referral institutions from October 2016 to January 2022. Results: SNP-array revealed that 20 fetuses had copy number variation (CNV) in the 16p13.11 region, out of which 5 had 16p13.11 microdeletion and the rest showed microduplication, along with different ultrasound phenotypes. Furthermore, 4/20 cases demonstrated structural abnormalities, while the remaining 16 cases were atypical in ultrasound. Taken together, 16p13.1 microdeletion was closely related to thickened nuchal translucency, while 16p13.11 microduplication was more closely associated with echogenic bowel. Only 5/15 fetuses were verified by pedigree, with one case of 16p13.11 microdeletion being de novo, and the other cases of 16p13.11 microduplication were inherited from one parent. In 4/20 cases, the pregnancy was terminated. Except for one case with short stature and another one who underwent lung cystadenoma surgery, no abnormalities were reported in the other cases during follow-up. Conclusion: Fetuses with 16p13.11 microdeletion/microduplication had no characteristic phenotype of intrauterine ultrasound and was in good health after birth, thus providing a reference for the perinatal management of such cases. [ABSTRACT FROM AUTHOR]

Background: The etiology of fetal growth restriction (FGR) is complex and currently, there is a paucity of research about the genetic etiology of fetal growth restriction. We investigated the genetic associations and pregnancy outcomes in cases of fetal growth restriction.Methods: A retrospective analysis of 210 pregnant women with fetal growth restriction was performed using karyotype analysis and single nucleotide polymorphism arrays (SNP-array). The differences in pathogenic copy number variation (CNV) detected by the two methods were compared. At the same time, the fetuses were divided into three groups: isolated FGR (n = 117), FGR with ultrasonographic soft markers (n = 48), and FGR with ultrasonographic structural anomalies (n = 45). Further, the differences in pathogenic copy number variations were compared among the groups.Results: The total detection rate of pathogenic CNVs was 12.4% (26/210). Pathogenic copy number variation was detected in 14 cases (6.7%, 14/210) by karyotype analysis. Furthermore, 25 cases (11.9%, 25/210) with pathogenic CNVs were detected using the SNP-array evaluation method. The difference in the pathogenic CNV detection rate between the two methods was statistically significant. The result of the karyotype analysis and SNP-array evaluation was inconsistent for 13 cases with pathogenic CNV. The rate of detecting pathogenic CNVs in fetuses with isolated FGR, FGR combined with ultrasonographic soft markers, and FGR combined with ultrasonographic structural malformations was 6.0, 10.4, and 31.1%, respectively, with significant differences among the groups. During the follow-up, 35 pregnancies were terminated, two abortions occurred, and 13 cases were lost to follow-up. Of the 160 deliveries, nine fetuses had adverse pregnancy outcomes, and the remaining 151 had normal postnatal growth and developmental assessments.Conclusions: Early diagnosis and timely genomic testing for fetal growth restriction can aid in its perinatal prognosis and subsequent intervention. [ABSTRACT FROM AUTHOR]

Smith-Magenis syndrome and Potocki-Lupski syndrome are rare autosomal dominant diseases. Although clinical phenotypes of adults and children have been reported, fetal ultrasonic phenotypes are rarely reported. A retrospective analysis of 6,200 pregnant women who received invasive prenatal diagnosis at Fujian Provincial Maternal and Child Health Hospital between October 2016 and January 2021 was performed. Amniotic fluid or umbilical cord blood was extracted for karyotyping and single nucleotide polymorphism array analysis. Single nucleotide polymorphism array analysis revealed six fetuses with copy number variant changes in the 17p11.2 region. Among them, one had a copy number variant microdeletion in the 17p11.2 region, which was pathogenically analyzed and diagnosed as Smith-Magenis syndrome. Five fetuses had copy number variant microduplications in the 17p11.2 region, which were pathogenically analyzed and diagnosed as Potocki-Lupski syndrome. The prenatal ultrasound phenotypes of the six fetuses were varied. The parents of two fetuses with Potocki-Lupski syndrome refused verification. Smith-Magenis syndrome in one fetus and Potocki-Lupski in another were confirmed as de novo. Potocki-Lupski syndrome in two fetuses was confirmed to be from maternal inheritance. The prenatal ultrasound phenotypes of Smith-Magenis syndrome and Potocki-Lupski syndrome in fetuses vary; single nucleotide polymorphism array analysis is a powerful diagnostic tool for these diseases. The ultrasonic phenotypes of these cases may enrich the clinical database. [ABSTRACT FROM AUTHOR]

Background: The current gold standard of karyotype analysis for prenatal diagnosis of fetuses with central nervous system (CNS) abnormalities has some limitations. Here, we assessed the value of single nucleotide polymorphism (SNP) arrays as a diagnostic tool. Methods: The results of prenatal diagnosis of 344 fetuses with CNS abnormalities as determined by ultrasonographic screening were retrospectively analyzed. All fetuses underwent chromosomal karyotype analysis and genome-wide SNP array analysis simultaneously. The resultant rates and frequencies of genomic abnormalities were compared. Results: Karyotype analysis found 45 (13.2%) abnormal CNS cases, while SNP array found 60 (17.4%) cases. SNP array detected 23 (6.7%) cases of submicroscopic abnormalities that karyotype analysis did not find. The detection rate of karyotype analysis was 8.1% in the group with isolated CNS anomalies, but 16.5% in the group with CNS abnormalities plus extra ultrasound anomalies. Detection rates of SNP array were 12.4% and 20.8% in these two groups, respectively. Statistical analysis showed that the detection rates of both methods were significantly higher in the group with CNS malformations and other ultrasound anomalies than in the group with isolated CNS anomalies. Abnormal chromosomes were detected most frequently in fetuses with holoprosencephaly. Conclusion: Genome-wide SNP array technology can significantly improve the positive detection rate of fetuses with CNS abnormalities. Combining karyotype analysis and SNP array technology is recommended for detecting the development of fetuses with abnormal CNS. [ABSTRACT FROM AUTHOR]

aimed to evaluate the genetic anomalies of fetuses with CPC using single nucleotide polymorphism (SNP) array analysis, as well as their obstetrical outcomes. Patients and Methods: Among 201 fetuses, 108, 69, and 24 had isolated CPC (iCPC), CPC with sonographic soft markers, and CPC with sonographic structural malformations, respectively. All fetuses underwent conventional karyotyping analysis and SNP array analysis. Results: Among 201 fetuses with CPC, 15 had chromosomal abnormalities (7.5%, 15/201), including nine fetuses with trisomy 18. Further, SNP array results were consistent with the conventional karyotype analysis and additionally revealed 6.0% (12/201) abnormal copy number variations (CNVs). The rates of pathogenic CNVs in fetuses with iCPC, CPC combined with sonographic soft markers, and CPC combined with sonographic structural malformations were 6.5%, 6.0%, and 45.8%, respectively, with significant differences among the groups. Conclusion: The results of the SNP array affected the obstetrical outcomes. CPC is thus associated with pathogenic CNVs in approximately 10.9% of cases. Therefore, SNP array should be offered for prenatal testing of fetuses with CPC. [ABSTRACT FROM AUTHOR]

Background: Echogenic intracardiac focus (EIF) is a common ultrasound finding during pregnancy. However, the correlation between fetal EIF and cardiac abnormality remains in dispute until now. The study aimed to examine the association of fetal EIF with chromosomal abnormality by means of chromosomal microarray analysis (CMA). Materials and Methods: A total of 192 pregnant women with fetal EIF undergoing amniocentesis or umbilical cord blood puncture were recruited and assigned into groups A (8 cases with isolated EIF alone), B (75 cases with EIF and other cardiac malformations) and C (109 cases with EIF and extracardiac malformations). All fetuses underwent karyotyping analysis and CMA simultaneously. The detection of chromosomal abnormality and copy number variations (CNVs) were compared. Results: Chromosomal karyotyping identified 5 fetuses with chromosomal abnormality, including 3 cases with trisomy 21, one fetus with Turner's syndrome, and one fetus with chromosome 8 mosaicism, while CMA detected 6 additional fetuses with CNVs, including 2 fetuses with pathogenic CNVs and 4 fetuses with variants of uncertain significance (VOUS). There was no significant difference among groups A (0), B (5.33%) and C (6.42%) in terms of the prevalence of chromosomal abnormality (P> 0.05). Among the 4 fetuses with VOUS, pregnancy continued in 2 fetuses, and pregnancy was terminated in other 2 fetuses. Conclusion: An isolated EIF may not correlate with chromosomal abnormality. However, CMA is recommended in fetuses with CMA complicated by other abnormal cardiac ultrasound findings, which facilitates the prediction of fetal outcomes during the genetic counseling and precision assessment of prognosis. [ABSTRACT FROM AUTHOR]

Background: Fetal echogenic bowel (FEB) is associated with an increased risk of poor pregnant outcomes; however, karyotyping fails to detect copy number variations (CNVs) in FEB. This study aimed to evaluate the performance of chromosomal microarray analysis (CMA) for detection of FEB. Methods: The medical records of 147 pregnant women with FEB recruited during December 2015 to December 2018 were retrospectively reviewed, and prenatal samples were collected for karyotyping and CMA. The detection of chromosomal abnormality was compared between karyotyping and CMA. Results: Karyotyping identified eight cases with abnormal karyotypes (5.44% prevalence), including four fetuses with pathogenic aneuploidy, three with chromosome polymorphism and one with balanced chromosome translocation. CMA identified 13 abnormal CNVs (8.84% prevalence), including 4 fetuses with pathogenic aneuploidy as detected by karyotyping and 9 additional CNVs with normal karyotypes; however, CMA failed to detect chromosome polymorphism and balanced chromosome translocation. In fetuses with isolated FEB, no cases presented pathogenic findings and CMA detected two cases with variants of uncertain significance (VOUS). In cases presenting FEB along with other ultrasound abnormalities, CMA detected three cases with pathogenic CNVs and four cases with VOUS in addition to four cases with aneuploidy. There was no significant difference in the detection of abnormal CNVs between the fetuses with echogenic bowel alone and along with other ultrasound abnormalities (10% vs 8.67%, P > 0.05). Except 9 fetuses lost to the follow-up, the other 138 fetuses with echogenic bowel were successfully followed up. Pregnancy was terminated in 5 fetuses with chromosomal abnormality, 2 with pathogenic CNVs and 1 with VOUS, and other 16 with normal karyotypes and CMA findings but showing ultrasound abnormalities or multiple malformations. Conclusion: Isolated FEB is associated with a good prognosis, and a satisfactory pregnant outcome is expected for fetuses with echogenic bowel that are negative for chromosomal anomalies and other severe structure abnormalities. CMA shows an important value in the genetic diagnosis of FEB. As a supplement to karyotyping, CMA may improve the accuracy of prenatal diagnosis of fetal intestinal malformations in pregnant women with FEB. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown a strong correlation between fetal nasal bone hypoplasia and chromosomal anomaly; however, there is little knowledge on the associations of fetal nasal bone hypoplasia with chromosomal microdeletions and microduplications until now. Chromosomal microarray analysis (CMA) is a high-resolution molecular genetic tool that is effective to detect submicroscopic anomalies including chromosomal microdeletions and microduplications that cannot be detected by karyotyping. This study aimed to examine the performance of CMA for the prenatal diagnosis of nasal bone hypoplasia in the second and third trimesters. Subjects and Methods: A total of 84 pregnant women in the second and third trimesters with fetal nasal bone hypoplasia, as revealed by ultrasound examinations, were enrolled, and all women underwent karyotyping and CMA with the Affymetrix CytoScan 750K GeneChip Platform. The subjects included 32 cases with fetal nasal bone hypoplasia alone and 52 cases with fetal nasal bone hypoplasia combined with other ultrasound abnormalities, and the prevalence of genomic abnormality was compared between these two groups. Results: Karyotyping detected 21 cases of chromosomal anomaly in the 84 study subjects (21/84, 25%), including trisomy 21 (14 cases), trisomy 18 (3 cases), 46, del (4)(p16) karyotype (2 cases), 47, XYY syndrome (1 case) and 46, XY, del (5) (p15) karyotype (1 case). CMA detected additional four fetuses with pathogenic copy number variations (CNVs) and six fetuses with uncertain clinical significance (VOUS). No significant difference was detected in the prevalence of genomic abnormality in fetuses with nasal bone hypoplasia alone and in combination with other ultrasound abnormalities (13/32 vs 18/52; χ2 = 0.31, P > 0.05). The pregnancy was terminated in 21 fetuses detected with chromosomal abnormality and 4 fetuses detected with pathogenic CNVs. Among the other six fetuses detected with VOUS, the parents chose to continue the pregnancy, and the newborns all had normal clinical phenotypes. Conclusion: In addition to chromosomal abnormalities identified in 21 fetuses by karyotyping, CMA detected additional 10 fetuses with abnormal CNVs (10/84, 11.9%) in the study population. CMA is a promising powerful tool for prenatal diagnosis that may provide valuable data for the accurate assessment of fetal prognosis and the decision of pregnancy continuation during the prenatal clinical counseling. [ABSTRACT FROM AUTHOR]

aimed to examine the effectiveness of the SNP array for the prenatal diagnosis of congenital heart disease (CHD) screened by echocardiography. Patients and Methods: A total of 356 pregnant women with fetal congenital heart malformations revealed by echocardiography at the Center for Prenatal Diagnosis of Fujian Maternal and Children Hospital during the period from November 2016 through July 2019 were recruited. The fetuses were assigned into three cohorts, including 142 with a single cardiac malformation, 106 with multiple cardiac malformations and 108 with cardiac and extracardiac malformations. All fetuses underwent chromosomal karyotyping and SNP array simultaneously, and the effectiveness of the SNP array for the prenatal diagnosis of CHD was evaluated. Results: The overall prevalence of abnormal karyotypes was 9.3% among the 356 fetuses with CHD, and a higher proportion was found in fetuses with cardiac and extracardiac malformations (18.5%) than in those with single (5.6%) or multiple cardiac malformations (4.7%) (P< 0.05). Consistent with karyotype analysis, SNP array detected an additional 25 fetuses with pathogenic copy number variations (CNVs), seven with variant of unknown significance (VOUS) and seven with benign CNVs, and a lower proportion of abnormal CNV was found in fetuses with a single cardiac malformation (4.2%) than in those with multiple cardiac malformations (9.4%) or cardiac and extracardiac malformations (14.8%) (P< 0.05). Among the 33 fetuses with chromosomal abnormality, postnatal follow-up showed termination of pregnancy in 25 with pathogenic CNVs, one with VOUS, and six with normal karyotypes and SNP array findings but severe multiple malformations by ultrasonography. Conclusion: SNP array increases the overall detection of abnormal CNVs by 9%, which improves the detection of CNVs associated with CHD. SNP array may serve as a tool for prenatal diagnosis of CHD that facilitates the discovery of pathogenic genes associated with CHD and provide valuable insights into the precision assessment of fetal prognosis during the prenatal counseling. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20–30% of all congenital malformations. Within the CAKUT phenotypic spectrum, renal hypodysplasia (RHD) is particularly severe. This study aimed to evaluate the applicability of single-nucleotide polymorphism (SNP) array test in prenatal diagnosis of RHD for improving prenatal genetic counseling and to search for evidence of a possible causative role of copy-number variations (CNVs) in RHD. Results: We performed a systematic survey of CNV burden in 120 fetuses with RHD: 103 cases were isolated RHD and 17 were non-isolated RHD. Single-nucleotide polymorphism (SNP) array test was performed using the Affymetrix CytoScan HD platform. All annotated CNVs were validated by fluorescence in situ hybridization. We identified abnormal CNVs in 15 (12.5%) cases of RHD; of these CNVs, 11 were pathogenic and 4 were variants of uncertain significance. The detection rate of abnormal CNVs in non-isolated RHD was higher (29.4%, 5/17) than that in isolated RHD (9.7%, 10/103) (P = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test. Conclusions: The variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the applicability of chromosomal microarray analysis (CMA), rather than traditional chromosome analysis, in prenatal diagnosis of ventricular septal defects (VSDs) for superior prenatal genetic counseling and to reveal a potential correlation between submicroscopic chromosomal aberrations and VSDs. Results: Among the 151 VSD cases, 79 (52.3%) had isolated defects and 72 (47.7%) had additional ultrasound anomalies. Karyotype analysis identified 16 chromosomal abnormalities. Besides the 14 cases of chromosome abnormalities consistent with karyotype analysis, CMA identified an additional 20 cases (13.2%) of abnormal copy number variations (CNVs), of which 13 were pathogenetic CNVs, 5 were variations of uncertain clinical significance (VOUS) and 2 were benign CNVs. The detection rate of pathogenic CNVs in non-isolated-VSDs was significantly higher than that in isolated-VSDs (36.1% (26/72) vs. 1.3% (1/79), p = 0.001). We also found that CMA results indicating pathogenic abnormalities affected the rate of pregnancy termination. Conclusions: This study showed that CMA combined with cytogenetic analysis is particularly effective in identifying CNVs in fetuses with VSDs and can have an effect on obstetrical outcomes. The elucidation of the etiology of VSDs suggested that gene mutations or other factors may be implicated. [ABSTRACT FROM AUTHOR]