Search

Abstract Background The incidence of CHD is the highest among birth defects and is increasing year to year. CHD seriously harms the health of infants and young children and presents a large economic burden to families and society. The pathogenesis of CHD and preventive measures are the focus of current research. Our research aimed to explore the intervention effect of folic acid on heart abnormalities resulting from sodium arsenic (NaAsO2) exposure during the periconception period. Methods Sixty 35-day-old female SD rats were randomly divided into 5 groups with 12 rats in each group. Group A was the control group. The rats were given distilled water and ordinary chow. The rats in group B were given distilled water containing 75 mg/L NaAsO2 and ordinary chow. The rats in groups C, D, and E were given distilled water containing 75 mg/L NaAsO2 and chow containing 0.53 mg/kg, 5.3 mg/kg, and 10.6 mg/kg folic acid, respectively. The general condition of the embryos and the histopathology of the embryonic hearts were examined. The acetylation levels of histone H3K9 in heart tissues and the expression levels of Mef2C (which is related to heart development) were observed. Results The embryo weight and placental weight of groups B-E were significantly lower than those of group A (P

Objective: To investigate the ultrasonographic findings and genetic testing methods for fetuses carrying copy number variants (CNVs) of 7q11.23 region., Methods: Prenatal cases with 7q11.23 microdeletion/microduplication detected by single nucleotide polymorphism array (SNP array) from January 2016 to June 2020 were retrospectively analyzed, including fetal ultrasound, chromosomal karyotype, SNP array, pregnancy outcome and follow-up. Literature on 7q11.23 CNVs identified upon prenatal diagnosis was also reviewed., Results: Five fetuses were found with 7q11.23 CNVs, including 3 microdeletions and 2 microduplications. Of them, 4 had ultrasonographic anomalies. The karyotypes of all fetuses were normal. Of three 7q11.23 microdeletions, two were de novo, while the remaining one couple did not accept parental verification. Of two 7q11.23 microduplications, one was de novo and the another was inherited from a phenotypic normal father. Three 7q11.23 microdeletions and one de novo 7q11.23 microduplication were electively aborted. One fetus carrying paternally inherited 7q11.23 microduplication was delivered full term. Follow-up found the infant had a normal phenotype., Conclusion: Fetuses with 7q11.23 microdeletions or microduplications showed phenotypic heterogeneity. SNP array can accurately detect 7q11.23 CNVs, thereby provide accurate information for prenatal diagnosis and genetic counseling.

Objective: To investigate the clinical features of fetuses with Wolf-Hirschhorn syndrome(WHS) and explore the diagnostic methods and prenatal ultrasound characteristics and provide evidence for prenatal genetic counseling., Methods: We retrospectively analyzed 5 cases of WHS fetuses diagnosed from March 2016 to February 2020, and analyzed the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) of the fetuses., Results: Five cases of WHS were detected by CMA, four cases were detected by karyotype analysis. Prenatal ultrasound revealed 4 abnormalities, of which 3 had intrauterine growth restriction, and only 1 had abnormalities of the maxillofacial region. The sequence of the fragments was 4p16.3p16.1 with a loss of 6.5 Mb, 4p16.3p15.32 with a loss of 15.6 Mb combined with 2p25.3 increased by 906kb, 4p16.3p15.31 with a loss of 20.4 Mb, 4p16.p15.1 with a loss of 35 Mb and 4p16.3p14 with a loss of 37 Mb., Conclusion: Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.

Objective: To evaluate the efficacy of non-invasive prenatal screening (NIPS) for fetal sex chromosome anomalies., Methods: A retrospective analysis was carried out for 20 802 women undergoing NIPS screening. For 165 cases suspected for fetal sex chromosomal anomalies, the results of invasive prenatal diagnosis were obtained., Results: Among the 165 cases suspected for fetal sex chromosome anomalies, 129 have accepted invasive prenatal diagnosis, and 45 were confirmed, which yielded a positive predictive value of 34.88%. These included 16 cases of 47,XYY, 10 cases of 47,XXY, 6 cases of 45,X/46,XX, 5 cases of 47,XXX, 3 cases of 45,X, 1 case of 45,X/46,X,i(X)(q10), 1 case of 45,X/46,X,del(X)(q22), 1 case of 46,X,del(X)(q22), 1 case of 46,X,del(X)(p11) and 1 case of Xp22.31 1.2 Mb deletion., Conclusion: NIPS has limited value for detecting fetal sex chromosome anomalies. Karyotyping analysis combined with other diagnostic techniques can offer effective prenatal diagnosis for suspected cases.

Objective: To assess the impact of confined placental mosaicism (CPM) on non-invasive prenatal testing (NIPT) and pregnancy outcomes., Methods: Copy number variation sequencing (CNV-seq) and single nucleotide polymorphism array (SNP-array) were carried out on placental specimen sampled from eight pregnancies with confirmed false-positive NIPT results. The impact of CPM on NIPT and pregnancy outcomes were analyzed based on the laboratory tests and clinical characteristics., Results: Five of the eight cases with false-positive NIPT results were proven to be CPM involving trisomy 9, 13, 21, 22, and X, respectively. The mosaic ratios for different placental regions have varied from 4% to 80%. Two fetuses with confirmed CPM showed fetal growth restriction (FGR) and additional ultrasound abnormalities, 1 fetus showed only FGR. The remaining two fetuses showed normal growth., Conclusion: NIPT is highly sensitive to CPM, whilst CPM is an important cause for false-positive NIPT result. CPM may be associated with FGR. Investigation of the presence of CPM is important for both pre- and post-test genetic counseling and management of the pregnancy.

Multiple molecular tests are currently needed for accurate carrier testing for thalassemia. Therefore, long-molecule sequencing (LMS) was evaluated as an alternate on the PacBio Sequel platform for genotyping carriers of α-thalassemia or β-thalassemia. Multiplex long PCR was used to generate representative amplicons for the α (HBA1/2) and β (HBB) gene loci. Following LMS, circular consensus sequencing reads were aligned to the hg19 reference genome and variants called using FreeBayes software version 1.2.0. In a blinded study of 64 known carrier samples, all HBA1/2 and HBB variants detected by LMS were concordant with those independently assigned by targeted PCR assays. For HBA1/2 carrier samples, LMS accurately detected the common South East Asian, -α3.7, and -α4.2 deletions and four different rare single-nucleotide variants (SNVs). For HBB carrier samples, LMS accurately detected the most common Chinese insertion and deletion variant c.126_129delCTTT and 14 different SNVs/insertions and deletions and could discriminate compound heterozygous SNVs (trans configuration) and identify variants linked to benign SNPs (cis configuration). Overall, LMS displayed the hallmarks of a scalable, accurate, and cost-effective genotyping method. With further test coverage to additionally include detection of other clinically significant HBA1/2 copy number variations, such as the Thai, Mediterranean, and Filipino deletions, LMS may eventually serve as a comprehensive method for large-scale thalassemia carrier screening., (Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

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.

Alpha (α)-thalassemia (thal) is a common single-gene genetic disease in southern China, which may cause Hb Bart's hydrops fetalis and Hb H disease. In α + thal, one of the α genes is inactivated, due either to a deletion (-α) such as the rightward deletion (-α 3.7 ) and leftward deletion (-α 4.2 ), or to another form of mutation (α T α), such as the Hb Constant Spring (α CS α). In this study, three probands from three Chinese families in Fujian Province showed HbH disease traits, while their common genotypes of α-thal were -- SEA /-- SEA at a routine analysis. In doing so, we further found a rare 27.6 kb deletion on the α-globin gene cluster in the three probands by MLPA (multiplex ligation-dependent probe amplification) and Sanger DNA sequencing, and its breakpoints were detected to lie between coordinates 9079 and 36718 with a total of 27,640 nucleotides deletion. The accurate genotypes of the three probands were -α 27.6 /-- SEA , which led to a very mild hemoglobin H (HbH) disease phenotype with low MCV, MCH, and HbA2 levels. Phenotypic analysis on the heterozygote of this deletion revealed it as α + mutation. In conclusion, we report a rare α-thal deletion, -α 27.6 , in three Chinese families from Fujian Province. Our study extends the spectrum of the α-thal mutation in the Chinese population. It is necessary to increase awareness of the rare α-thal mutation and to increase its detection, which will prove valuable in genetic counseling and prenatal diagnosis in Fujian Province., Competing Interests: None., (IJCEP Copyright © 2018.)

Background: To investigate impacts of sodium arsenic (NaAsO 2 ) on embryonic cardiac development in rats and evaluate the protective role of folate in NaAsO 2 exposure rats., Methods: We divided 90 female rats randomly into 9 groups. Group A was the control; group B-F were the animals fed with NaAsO 2 in a series of increased doses, corresponding to 9.4 mg/L, 18.8 mg/L, 37.5 mg/L, 75 mg/L and 150 mg/L, respectively; group G-I were fed with 75 mg/L of NaAsO 2 , in addition of folate with doses of 0.53 mg/kg, 5.3 mg/kg, and 10.6 mg/kg, respectively. Their fetus' general development and cardiovascular systems were examined. Nkx2.5, GATA4, TBX5 gene and protein expression were measured., Results: Relatively to group A, arsenic treated group C-F rats generated significantly lower weight of fetus and placenta (P<0.05), whereas the folate-treated groups H and I were significantly heavier than the arsenic-treated group E (P<0.05). We observed that incidences of cardiac malformations were significantly greater in arsenic-treated group E and F than group A (P<0.05). We found that the Nkx2.5 and GATA4 protein expression in the fetal hearts were downregulated in group B-F compared to group A. But the expression of them was significantly upregulated in group H-I relatively to group E (P<0.05). Moreover, the TBX5 gene expression was increased in both group D-F and G-I when they were compared to group A or group E, respectively (P<0.05)., Conclusion: NaAsO 2 induce embryonic cardiac defection and folate supplement alleviate this impairment through modulation of the Nkx2.5, GATA4 and TBX5 gene expression., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: To report on prenatal diagnosis of a fetus with Miller-Dieker syndrome (MDS) and explore its genotype - phenotype correlation., Methods: Chromosome karyotyping, bacterial artificial chromosome on beads (BACs-on-Beads, BoBs), fluorescence in situ hybridization (FISH), and single nucleotide polymorphism microarray (SNP array) were applied in conjunction for the prenatal diagnosis of a fetus with abnormal ultrasound findings., Results: A 17p13.3 microdeletion was detected with the BoBs assay, and the result was confirmed by FISH. With the SNP array, the deletion was mapped to chromosome 17, with its range determined to be 5.2 Mb. On high-resolution banding analysis and BoB assay, the deletion was not found in either parent., Conclusion: The combined use of BoBs, FISH and SNP array has enabled prenatal diagnosis of a fetus with MDS. Attention should be paid to microdeletions and microduplications which can be missed by conventional chromosomal karyotyping analysis.