[Analysis of genome copy number variations in fetuses with isolated ventricular septal defect and a literature review].

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION: Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.

[Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with Bainbridge-Ropers syndrome].

OBJECTIVE: To explore the clinical features and genetic basis for a child with Bainbridge-Ropers syndrome (BRPS). METHODS: Clinical data of the child were retrospectively analyzed. Copy number variation sequencing (CNV-seq) and trio based whole exome sequencing (trio-WES) were carried out. Prenatal diagnosis was provided for a at risk fetus from the pedigree, and genotype phenotype correlation was summarized through a literature review. RESULTS: The proband, a 6-year-old boy, has presented with feeding difficulties, specific craniofacial features, global developmental delay and intellectual disability, which has not improved after rehabilitation treatment. CNV-seq analysis of the patient showed no obvious abnormalities. A de novo heterozygous truncating variation, c.1448dupT (p.T484Nfs*5), was identified in the ASXL3 gene by trio-WES, which was a previously reported pathogenic variant. So far 14 Chinese patients with BRPS and ASXL3 variants have been reported. All patients have shown specific craniofacial features and delayed motor and speech development, and harbored 12 loss of function ASXL3 variants, which were de novo in origin and have clustered in exons 11 and 12 of the ASXL3 gene. CONCLUSION: The heterozygous frameshift c.1448dupT (p.T484Nfs*5) variant of the ASXL3 gene probably underlay the disorder in this patient. BRPS should be considered in infants with feeding difficulties, special craniofacial features, global developmental delay and hand anomalies, and WES can help to delineate the pathogenesis and establish the definite diagnosis.

[Analysis of a case with Mowat-Wilson syndrome due to nonsense variant of ZEB2 gene].

OBJECTIVE: To explore the genetic basis for a girl with distinctive facial features, epilepsy, intellectual disability, chronic constipation and hypopigmentation of neck and upper extremities. METHODS: Whole exome sequencing was carried out for the proband. Candidate variant was verified by Sanger sequencing. RESULTS: The proband was found to harbor a heterozygous nonsense c.586G>T (p.Glu196*) variant of the ZEB2 gene, which was unreported previously. The variant was not detected in either parent. CONCLUSION: The ZEB2 gene c.586G>T (p.Glu196*) variant probably underlay the Mowat-Wilson syndrome in this patient. Hypopigmentation in the neck and upper extremities may be related to Mowat-Wilson syndrome. Prenatal diagnosis was recommended for subsequent pregnancies.

[Expert consensus on the scientific management of serum prenatal screening].

Serum prenatal screening in the second trimester is currently the prenatal screening method with the highest population coverage rate, and large-scale serum prenatal screening has become a trend. The Medical Genetics Committee of the Chinese Eugenics Science Association organized some experts in prenatal screening in China to jointly draft the "Expert Consensus on the Scientific Management of Serum Prenatal Screening", which focusing on the organization and management of large-scale serum prenatal screening and quality control in the laboratory, for reference by domestic counterparts.

Association between NME1 polymorphisms and cancer susceptibility: A meta-analysis based on 1644 cases and 2038 controls.

The association between polymorphisms in the nucleoside diphosphate kinase 1 (NME1) gene and overall risk of cancer remains to be elucidated. Here, we performed a meta-analysis of the association between rs16949649, rs2302254, and rs34214448 polymorphisms in the NME1 gene and cancer risk. PubMed, Web of Science, and CNKI databases (as of June 6, 2017) were searched. Eight studies, encompassing 1644 cases and 2038 controls, were selected. The results revealed no significant relationship between NME1 polymorphisms and overall cancer susceptibility. Interestingly, the rs16949649 polymorphism was associated with increased susceptibility to gynecological cancer (heterozygous model: odds ratio [OR] = 1.74, 95% confidence interval [CI] = 1.06-2.86, P = 0.029). The rs2302254 polymorphism was linked to decreased susceptibility to gastric cancer in the other groups (recessive model: OR = 0.53, 95% CI = 0.28-0.98, P = 0.045). The rs34214448 polymorphism correlated significantly with increased susceptibility to non-small cell lung cancer according to all genetic models (P < 0.05) and was linked to decreased risk in cervical cancer (recessive model: OR = 0.51, 95% CI = 0.27-0.94, P = 0.031). Thus, our meta-analysis found rs16949649 associated with increased susceptibility to gynecological cancer and rs2302254 was linked to reduced gastric cancer risk; additional, larger studies are required to confirm these findings.

Efficacy and Safety of Belimumab Plus Standard Therapy in Patients With Systemic Lupus Erythematosus: A Meta-analysis.

PURPOSE: The treatment of belimumab plus standard therapy in patients with systemic lupus erythematosus (SLE) has been studied extensively in recent years. Our aim was to estimate the efficacy and safety of this therapy compared with placebo plus standard therapy in patients with SLE. METHODS: PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), and Wanfang Database (Chinese) were searched for all randomized clinical trials that mainly studied the efficacy and safety of belimumab plus standard therapy before June 2015. We extracted or calculated the rate of the SLE Response Index and adverse event rate at 52 weeks in all the included studies. The odds ratio (OR) with 95% CI between the 2 groups in this meta-analysis was conducted by using a random-effects model. Sensitivity and publication bias analyses were also performed. All statistical tests were performed by using Stata software version 12.0 (StataCorp., College Station, Texas). FINDINGS: In the overall samples (4 studies, N = 4692 ), a significantly higher SLE Response Index rate at 52 weeks was found in belimumab plus standard therapy group compared with the placebo plus standard therapy group in all studies (OR = 1.49; 95% CI, 1.26-1.77 ; P < 0.001 ). When assessed with the incidence of serious adverse events, the data revealed that there was no significant difference between the 2 groups, with pooled OR = 1.08; 95% CI, 0.83-1.39; P = 0.573; OR = 1.23; 95% CI, 1.02-1.48; P = 0.029; and OR = 1.07; 95% CI, 0.88-1.29; P = 0.506. IMPLICATIONS: The results suggest that treatment with belimumab plus standard therapy is more effective than placebo plus standard therapy in SLE patients, which represents major progress in the treatment of SLE. Regardless of the statistical analyses, further research is necessary to optimize treatment effects.

MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF.

MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.