A Novel EYA1 Mutation Causing Alternative RNA Splicing in a Chinese Family With Branchio-Oto Syndrome: Implications for Molecular Diagnosis and Clinical Application

Anhai Chen,Chufeng He,Yong Feng,Jie Ling,Xin Peng,Xianlin Liu,Shuang Mao,Yongjia Chen,Mengyao Qin,Shuai Zhang,Yijiang Bai,Jian Song,Zhili Feng,Lu Ma,Dinghua He,Lingyun Mei1 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.4

Objectives. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However,few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenicfactors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in thesepatients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the ge-netic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individualswithin the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis andclassified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing wasverified through a minigene assay. The predicted three-dimensional protein structure and biochemical experimentswere used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was fol-lowed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results. A novel heterozygous EYA1 splicing variant (c.1050+4 A >C) was identified and classified as pathogenic (PVS1(RNA),PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation mayimpair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellularmislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improvedhearing loss caused by bone-conduction abnormalities in the proband. Conclusion. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molec-ular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgeryprovides a reference for auditory rehabilitation in similar patients.

Efficacy and Safety of Neurokinin-1 Receptor Antagonists for Prevention of Chemotherapy-Induced Nausea and Vomiting: Systematic Review and Meta-analysis of Randomized Controlled Trials

Yuan, Dong-Mei,Li, Qian,Zhang, Qin,Xiao, Xin-Wu,Yao, Yan-Wen,Zhang, Yan,Lv, Yan-Ling,Liu, Hong-Bin,Lv, Tang-Feng,Song, Yong Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Objectives: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. Materials and Methods: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. Results: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, P<0.001), acute phase (85.1% vs 79.6%, P<0.001), and delayed phase (71.4% vs 58.2%, P<0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, P<0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, P<0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, P<0.001; occurrence of vomiting: 22.6% vs 38.9%, P<0.001; usage of rescue drugs: 23.5% vs 34.1%, P<0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. Conclusions: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.

Relations between Stress and Quality of Life among Women in Late Pregnancy: The Parallel Mediating Role of Depressive Symptoms and Sleep Quality

Han Zhang,Qi Zhang,Tingting Gao,Yixi Kong,Zeying Qin,Yueyang Hu,Ruilin Cao,Songli Mei 대한신경정신의학회 2019 PSYCHIATRY INVESTIGATION Vol.16 No.5

Objective: This study aims to examine the parallel multiple mediators of depressive symptoms and sleep quality in the relations between stress and physical health-related quality of life (PHQOL)/mental health-related quality of life (MHQOL) among the women in late pregnancy. Methods: Of 1120 pregnant women participated in the cross-sectional study which consisted of Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Pittsburgh Sleep Quality Index and MOS 12-item Short Form Health Survey. Parallel multiple mediator models were used to analyze the relations between stress, depressive symptoms, sleep quality and PHQOL/MHQOL. Results: The effect of perceived stress on PHQOL was partially through the indirect path of sleep quality (β=-0.061). But in the model for MHQOL, depressive symptoms and sleep quality played parallel mediators, and the indirect path effect of depressive symptoms (β=-0.179) was higher than sleep quality (β=-0.029). Conclusion: The findings contributed to the understanding about the influential mechanism of stress on PHQOL/MHQOL. And it reminded the importance of sleep quality and depressive symptoms for improving QOL in late pregnancy.

Identification, fine mapping and characterization of Rht-dp, a recessive wheat dwarfing (reduced height) gene derived from Triticum polonicum

Hou-Yang Kang,Li-Juan Lin,Zhi-Jian Song,Jing-Ya Yuan,Mei-Yu Zhong,Hai-Qin Zhang,Xing Fan,Li-Na Sha,Yi Wang,Li-Li Xu,Jian Zeng,Yong-Hong Zhou 한국유전학회 2012 Genes & Genomics Vol.34 No.5

Semi-dwarfism is an agronomically important trait in breeding for resistance to damage by wind and rain (lodging resistance)and for stable high yields. Dwarf Polish wheat (Triticum polonicum L., 2n = 4x = 28, AABB AS304) is a potential donor of dwarfing and other traits for common wheat improvement. A genetic analysis using an F2 population derived from a cross of AS304 and tall cultivar AS302 and derived F2:3 lines indicated that AS304 carries a recessive dwarfing gene, temporarily designated Rht-dp. Molecular markers and bulked segregant analysis were used to characterize and map the gene. Eight polymorphic SSR markers (Xwmc511, Xgwm495, Xgwm 113, Xgwm192, Xgpw7026, Xgpw3017, Xgpw1108 and Xgpw7521) on chromosome arm 4BS and two AFLP markers (M8/E5 and M4/E3) were mapped relative to the dwarfing locus. The closest linked markers, Xgpw3017 and M8/E5 at 0.5 and 3.5 cM, respectively, from Rht-dp will enable its marker assisted transfer to wheat breeding populations. Allelic tests indicated that Rht-dp was allelic to Rht-B1b; hence it may be an alternative allele at the Rht-B1 locus.

In Vitro Screening for Compounds Derived from Traditional Chinese Medicines with Antiviral Activities Against Porcine Reproductive and Respiratory Syndrome Virus

( Jia Cheng ),( Na Sun ),( Xin Zhao ),( Li Niu ),( Mei Qin Song ),( Yao Gui Sun ),( Jun Bing Jiang ),( Jian Hua Guo2 ),( Yuan Sheng Bai ),( Jun Ping He ),( Hong Quan Li ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.8

Seventeen compounds derived from traditional Chinese medicines (TCMs) were tested for their antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV) in vitro. Visualization with the cytopathologic effect (CPE) assay and the 3-(4, 5-dimethyithiazol- 2-yl)-2,5-diphenyltetrazolium bromide test were used to determine the 50% cytotoxic concentration (CC50) and 50% effective concentration (EC50) in cultured Marc-145 cells. Among the tested compounds, chlorogenic acid and scutellarin showed potential anti-PRRSV activity. The EC50 values were 270.8 ± 14.6 μg/ml and 28.21 ± 26.0 μg/ml and the selectivity indexes were >5.54 and 35.5, respectively. The time-of-addition and virucidal assay indicated that the anti-PRRSV activity of the two compounds could be due to their inhibiting the early stage of virus replication and/or inactivating the virus directly. The inhibition of the virus attachment was not observed in the adsorption inhibition assay. The inhibition ratios of chlorogenic acid and scutellarin were, respectively, 90.8% and 61.1% at the maximum non-cytotoxic concentrations. The results have provided a basis for further exploration of their antiviral properties and mechanisms in vivo. We believe that the chlorogenic acid and scutellarin have a great potential to be developed as new anti-PRRSV drugs for clinical application.