Analysis of deafness susceptibility gene of neonates in northern Guangdong, China.

This study aimed to explore the molecular epidemiology characteristics of deafness susceptibility genes in neonates in northern Guangdong and provide a scientific basis for deafness prevention and control. A total of 10,183 neonates were recruited between January 2018 and December 2022 at Yuebei People's Hospital. Among these, a PCR hybridization screening group of 8276 neonates was tested for four deafness genes: GJB2, SLC26A4, mtDNA, and GJB3 by PCR hybridization. Another group used next-generation sequencing (NGS) to detect genetic susceptibility genes in 1907 neonates. In PCR hybridization screening group, 346 (4.18%) of 8276 neonates were found to be carriers of the deafness gene. Among these, 182 (2.2%) had GJB2 variants, 114 (1.38%) had SLC26A4 variants, 35 (0.42%) had mtDNA variants, and 15 (0.18%) had GJB3 variants. In NGS Screening Group, 195 out of 1907 neonates were found to be carriers of the deafness gene, with a positive rate of 10.22%. Among these, 137 (7.18%) had GJB2 variants, 41 (2.15%) had SLC26A4 variants, 11 (0.58%) had mtDNA variants, and 6 (0.31%) had GJB3 variants. The prevalence of deafness gene variants was high in Northern Guangdong Province. The most common gene for deafness was GJB2, followed by SLC26A4 and mtDNA. GJB3 variants are rare. Compared with PCR hybridization method, NGS technology can expand the screening scope and greatly improve the detection rate of deafness genes. The c.109G>A of GJB2 was found to occur at a high frequency, which should be considered. Therefore, it is important to conduct neonatal deafness gene screening to prevent and control hereditary deafness.

Molecular characterization of hemoglobinopathies and thalassemias in Northern Guangdong Province, China.

ABSTRACT: To detect the molecular characterization of hemoglobinopathies and thalassemias in Northern Guangdong Province of China.We recruited 10,285 subjects who were screened for hemoglobin (Hb) variants and thalassaemia genotypes in the outpatient department of Yuebei People's Hospital from January 2018 to December 2020. The subjects collected venous blood samples for blood cell parameter analysis and Hb electrophoresis analysis. When the average red blood cell volume is <82 fL, or the average red blood cell Hb is <27 pg, or HbA2 > 3.5%, or HbA2 < 2.5%, or HbF > 2.0%, the screening is positive if one of them is satisfied. All subjects who were screened positive were tested for the thalassaemia gene by gap-polymerase chain reaction, PCR-based reverse dot blot, and DNA sequencing.Among all subjects screened, the overall prevalence of hemoglobinopathies and thalassemias were 0.46% (47/10,285) and 21.02% (2162/10,285) in Northern Guangdong Province. We found that Hb Q-Thailand is the most common, and other types of hemoglobinopathies are followed by Hb E, Hb New York, Hb G-Chinese, Hb G-Coushatta, Hb J-Bangkok, Hb J-Broussais, Hb Ottawa, and Hb G-Taipei. We identified 1340 cases (13.03%) of α-thalassemia, mainly includes --SEA deletion (71.64%), -α3.7 deletion (12.01%), -α4.2 deletion (4.78%). And identified 652 cases (6.34%) of ß-thalassemia, the most prevalent being CD 41/42(-TTCT) (35.89%), IVS-II-654 (C > T) (33.44%), CD 17 (A > T) (10.28%) and -28(A > G) (9.66%). Furthermore, there are 170 cases (1.65%) of α combined ß thalassaemia. In addition, we found a rare case with -80 (T > A) of ß-thalassemia. The results of this study found a high prevalence of hemoglobinopathies and thalassemias in Northern Guangdong Province, China. There were some differences molecular characterizations of thalassemia in different areas of China.Our results enriched the related information of hemoglobinopathies and thalassemias in the region, which provided valuable references for the prevention and control of thalassemia.

Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests.

PURPOSE: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. METHODS: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. RESULTS: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. CONCLUSION: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies-positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

Copy number variation profile in noninvasive prenatal testing (NIPT) can identify co-existing maternal malignancies: Case reports and a literature review.

OBJECTIVE: The coexistence of maternal malignancy and pregnancy has received increasing attention in Noninvasive prenatal testing (NIPT) studies. Malignancy in pregnant women potentially affects the copy number variation (CNV) profile in NIPT results. Only one case of hematologic cancer has been reported in a Hong-Kong pregnant women, and solid tumors have never been reported in pregnant Chinese women. CASE REPORT: The patients with dysgerminoma and cervical cancer showed aberrant chromosomal aneuploidies in NIPT and concordant patterns of genome disruption in tumor tissues. The genomic aberrations in the gastric cancer patient had similar copy number variation pattern of gastric cancer. CONCLUSION: The findings in this study and the literature review further validate the effect of maternal malignancy on the copy number variation profile in NIPT data and strengthen the possibility of detecting malignant tumors with NIPT in the future.

Prenatal diagnosis of Wolf-Hirschhorn syndrome: Ultrasonography and molecular karyotyping results.

OBJECTIVE: To present the experience on prenatal diagnosis of Wolf-Hirschhorn syndrome (WHS) to further delineate the fetal presentation of this syndrome. STUDY DESIGN: This was a retrospective analysis of ten pregnancies with fetal WHS identified by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal demographics, indications for invasive testing, sonographic findings, CMA results and pregnancy outcomes. RESULTS: Three cases were diagnosed at the first trimester because of an increased NT or cystic hygroma. The remaining seven cases were identified at late gestation for abnormal ultrasound findings. CMA revealed 4p deletions to be terminal in all of the ten cases. Deletion sizes ranged from 2.05 to 19.02 Mb. CONCLUSION: Prenatal findings such as increased NT, severe and early onset intrauterine growth retardation, and renal dysplasia or oligohydramnios should warrant the diagnosis of WHS and invasive testing using CMA.

[Multicenter analysis of risk factors and clinical characteristics of shoulder dystocia].

OBJECTIVE: To explore the risk factors and clinical characteristics of shoulder dystocia. METHODS: The data of 44 580 single pregnancy and full-term head delivery were colleceted in the Third Affiliated Hospital of Guangzhou Medical University, Nanfang Hospital, Shenzhen Nanshan Hospital, Peking University Shenzhen Hospital and Yue Bei People's Hospital from January 2008 to September 2013. Totally 116 cases of shoulder dystocia were defined as the shoulder dystocia group, and the others were in the control group. The clinical data of the two groups were analyzed retrospectively, including the maternal age, maternal height, pre-gestational body mass index, weight gain during pregnancy, gestational weeks, gravidity, parity, fundal height, fetal abdominal perimeter, shoulder dystocia medical history, macrosomia, gestational diabetes mellitus, pre-gestational diabetes mellitus, post-term pregnancy and the condition of labor stages. RESULTS: (1) The incidence of shoulder dystocia was 0.260% (116/44 580). The maternal age, pre-gestational body mass index and weight gain during pregnancy in the shoulder dystocia group were higher than those in the control group (all P < 0.01). While the maternal height, gestational weeks, gravidity, parity, fundal height, abdominal circumference in the two groups had no significant difference (all P > 0.05). (2) In the shoulder dystocia group, the incidence of shoulder dystocia medical history (11.21%, 13/116), macrosomia (13.79% , 16/116), pre-gestational diabetes mellitus (7.76% , 9/116), post-term pregnancy (10.34%, 12/116), prolongation of maximum acceleration phase (8.62%, 10/116) and prolongation of second labor stage (7.76%, 9/116) were different from those in the control group[1.43% ( 636/44 464), 1.48% (658/ 44 464), 0.57% ( 252/44 464), 1.15% (513/44 464),0.72% (322/44 464), 0.65% (289/44 464), respectively; all P < 0.05]. (3) Logistic regression analysis showed that the risk factors of shoulder dystocia were maternal age over thirty-five years (OR = 1.116, 95%CI: 1.022-2.445), pre-gestational body mass index more than 27 kg/m(2) (OR = 1.893, 95% CI: 1.358-2.228), weight gain more than 20 kg during pregnancy (OR = 2.031, 95% CI: 1.749-3.231), shoulder dystocia medical history (OR = 2.138, 95%CI:1.564-3.853), macrosomia (OR = 3.276, 95% CI:2.315- 4.638), pre-gestational diabetes mellitus (OR = 3.261, 95% CI:2.237- 4.943), post-term pregnancy (OR = 1.473, 95% CI:1.003-2.721), prolongation of the maximum acceleration phase (OR = 2.022, 95% CI:1.681- 3.732), prolongation of second labor stage(OR = 1.943, 95% CI:1.285- 3.215). CONCLUSION: Maternal age over thirty-five years old, pre-gestational body mass index more than 27 kg/m(2), weight gain more than 20 kg during pregnancy, shoulder dystocia medical history, macrosomia, pre-gestational diabetes mellitus, post-term pregnancy, prolongation of the maximum acceleration phase, and prolongation of second labor stage are risk factors and clinical characteristics of shoulder dystocia.

[Recombinant human epithelial growth factor accelerates healing of cervical erosion].

OBJECTIVE: To observe the effect of recombinant human epithelial growth factor (rhEGF) in promoting the healing of cervical erosion. METHODS: Forty-eight patients with cervical erosion were treated with rhEGF and 30 with 500 kHz high-frequency electromagnetic wave, and the effects of the therapies were compared in terms of healing of the cervical wound, healing time, volume of vaginal discharge and bleeding and the lasting time. RESULTS: In comparison with radiofrequency therapy, the healing of the lesion took significantly shorter time with rhEGF therapy, which also resulted in less vaginal discharge that lasted for shorter time without causing vaginal bleeding. CONCLUSION: rhEGF can obviously accelerate the healing of cervical erosion.

[Placental expression of human histocompatibility antigen-G mRNA in idiopathic fetal growth restriction and its relationship with pathological changes of placenta].

OBJECTIVE: To investigate the expressions of human histocompatibility antigen-G (HLA-G) mRNA in placenta of idiopathic fetal growth restriction (IFGR) and its relationship with pathogenesis of IFGR. METHODS: In situ hybridization was used to investigate the expression level and distribution of HLA-G mRNA in placentas of 20 cases of idiopathic IFGR and 28 cases of control group. HE stain was applied to observe the pathological changes of the placenta. RESULTS: (1) The incidence of placental pathological lesions in idiopathic IFGR (75%) was notably higher than those of the control group (18%), (chi2 = 15.67, P = 0.001). (2) In situ hybridization showed the positive expression rate of HLA-G mRNA in placenta of idiopathic IFGR was 45%, that of control group was 79%, with significant difference between the two groups (chi2 = 5.75, P = 0.017). HLA-G mRNA signal mainly expressed in cytotrophoblast and syncytiotrophoblast. (3) There was negative correlation between the expression rate of HLA-G mRNA and incidence of placental pathological lesions (r = -0.638, P = 0.008). CONCLUSIONS: There is a significant decrease in the expression of HLA-G mRNA in IFGR. HLA-G may play a role in the pathogenesis of IFGR.