Four mutations identified in Chinese families with autosomal dominant congenital cataracts by next-generation sequencing

Yang Xinyi,Zhao Zitong,Wang Chun,Wang Wenxuan,Zhang Lu 한국유전학회 2024 Genes & Genomics Vol.46 No.8

Background Congenital cataracts, which can arise due to a combination of factors like environmental influences and genetic predisposition, significantly impact children’s visual health globally. The occurrence rate of congenital cataracts varies from 0. 63 to 9.74 per 10,000 births. There are 7.4 instances per 10,000 children, with the highest occurrence seen in Asia. Symptoms of the disease include clouding of the lens and visual impairment. Timely identification of the condition plays a crucial role in the management and outlook of pediatric patients. Objective This investigation aimed to discover causative mutations in four separate Chinese family lineages. Methods The detailed clinical data and family history of four Chinese families with autosomal dominant congenital cataracts were carefully documented. Examination of the Whole Exome Sequencing was utilized to identify the genetic anomalies present in the familial cases. Subsequent validation of the identified mutations was carried out using PCR and Sanger sequencing. Following this, various computational predictive programs were utilized to evaluate how the mutations impact the structure and function of the protein. Results The sequencing results reveal four potential disease-causing mutations: c.436G > A (p.V146M) of CRYBB2 Family 1, c.26G > T (p.R9I) of GJA3 in family 2, c.227G > A (p.R76H) of GJA8 in family 3, c.-168G > T of FTL in family 4. Among them, the causative mutation in Family GJA3 is novel, and Family FTL is a rare cataract syndrome. These familial mutations showed complete co-segregation with the affected individuals, with no presence in unaffected family members or the 100 controls. Several bioinformatic prediction tools also support the likely pathogenicity of these mutations. Conclusion Our findings expand the mutational and phenotypic spectrum of genes associated with congenital cataracts and provide clues to the pathogenesis of congenital cataracts. These data also demonstrate the importance of NGS technology for the molecular diagnosis of congenital cataract patients. Background Congenital cataracts, which can arise due to a combination of factors like environmental influences and genetic predisposition, significantly impact children’s visual health globally. The occurrence rate of congenital cataracts varies from 0. 63 to 9.74 per 10,000 births. There are 7.4 instances per 10,000 children, with the highest occurrence seen in Asia. Symptoms of the disease include clouding of the lens and visual impairment. Timely identification of the condition plays a crucial role in the management and outlook of pediatric patients. Objective This investigation aimed to discover causative mutations in four separate Chinese family lineages. Methods The detailed clinical data and family history of four Chinese families with autosomal dominant congenital cataracts were carefully documented. Examination of the Whole Exome Sequencing was utilized to identify the genetic anomalies present in the familial cases. Subsequent validation of the identified mutations was carried out using PCR and Sanger sequencing. Following this, various computational predictive programs were utilized to evaluate how the mutations impact the structure and function of the protein. Results The sequencing results reveal four potential disease-causing mutations: c.436G > A (p.V146M) of CRYBB2 Family 1, c.26G > T (p.R9I) of GJA3 in family 2, c.227G > A (p.R76H) of GJA8 in family 3, c.-168G > T of FTL in family 4. Among them, the causative mutation in Family GJA3 is novel, and Family FTL is a rare cataract syndrome. These familial mutations showed complete co-segregation with the affected individuals, with no presence in unaffected family members or the 100 controls. Several bioinformatic prediction tools also support the likely pathogenicity of these mutations. Conclusion Our findings expand the mutational and phenotypic spectrum of genes associated with congenital cataracts and provide clues to the pathogenesis of congenital cataracts. These data also demonstrate the importance of NGS technology for the molecular diagnosis of congenital cataract patients.

Existence and uniqueness of solutions for a singular system of nonlinear fractional differential equations with integral boundary conditions

Lin Wang,Xinyi Lu 한국전산응용수학회 2013 Journal of applied mathematics & informatics Vol.31 No.5

In this paper, we study the existence and uniqueness of solutions for a singular system of nonlinear fractional differential equations with integral boundary conditions. We obtain existence and uniqueness results of solutions by using the properties of the Green's function, a nonlinear alternative of Leray-Schauder type, Guo-Krasnoselskii's fixed point theorem in a cone. Some examples are included to show the applicability of our results.

Shear bond strength of zirconia to resin: The effects of specimen preparation and loading procedure

Bingzhuo Chen,Lu Yang,Zhicen Lu,Hongliang Meng,Xinyi Wu,Chen Chen,Haifeng Xie 대한치과보철학회 2019 The Journal of Advanced Prosthodontics Vol.11 No.6

PURPOSE. Shear bond strength (SBS) test is the most commonly used method for evaluating resin bond strength of zirconia, but SBS results vary among different studies even when evaluating the same bonding strategy. The purpose of this study was to promote standardization of the SBS test in evaluating zirconia ceramic bonding and to investigate factors that may affect the SBS value of a zirconia/resin cement/composite resin bonding specimen. MATERIALS AND METHODS. The zirconia/resin cement/composite resin bonding specimens were used to simulate loading with a shear force by the three-dimensional finite element (3D FE) modeling, in which stress distribution under uniform/non-uniform load, and different resin cement thickness and different elastic modulus of resin composite were analyzed. In vitro SBS test was also performed to validate the results of 3D FE analysis. RESULTS. The loading flat width was an important affecting factor. 3D FE analysis also showed that differences in resin cement layer thickness and resin composite would lead to the variations of stress accumulation area. The SBS test result showed that the load for preparing a SBS specimen is negatively correlated with the resin cement thickness and positively correlated with SBS values. CONCLUSION. When preparing a SBS specimen for evaluating bond performance, the load flat width, the load applied during cementation, and the different composite resins used affect the SBS results and therefore should be standardized.

EXISTENCE AND UNIQUENESS OF SOLUTIONS FOR A SINGULAR SYSTEM OF NONLINEAR FRACTIONAL DIFFERENTIAL EQUATIONS WITH INTEGRAL BOUNDARY CONDITIONS

Wang, Lin,Lu, Xinyi The Korean Society for Computational and Applied M 2013 Journal of applied mathematics & informatics Vol.31 No.5

In this paper, we study the existence and uniqueness of solutions for a singular system of nonlinear fractional differential equations with integral boundary conditions. We obtain existence and uniqueness results of solutions by using the properties of the Green's function, a nonlinear alternative of Leray-Schauder type, Guo-Krasnoselskii's fixed point theorem in a cone. Some examples are included to show the applicability of our results.

Effect of Al2O3 Addition on Microwave Dielectric Properties of BaCo0.194Zn0.116Nb0.69O3 Ceramics

Peijun Liao,Tai Qiu,Jian Yang,Xinyi Lu 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.1

This study investigates the effects of Al2O3 addition on sintering, microstructures, phase formation and the microwave dielectric properties of BaCo0.194Zn0.116Nb0.69O3 (BCZN) ceramics prepared by the conventional solidstate route. Addition of low alumina content was found to effectively improve the Q×f value of BCZN ceramics. Addition of an appropriate amount of Al2O3 was found beneficial to the growth and uniformity of the ceramic grain, significantly improving the quality factor of BCZN ceramics. However, the performance of the ceramics deteriorated when an excessive secondary phase, inhomogeneous grain of small size and larger porosity were generated from the BCZN ceramic doped with excessive alumina. An optimum Q × f of 61056 GHz (f = 7.44 GHz) was obtained for the BCZN ceramic doped with 1 wt. % Al2O3 addition sintered at 1350°C for 3 h, which is markedly better than that of pure BCZN ceramic sintered at 1300°C for 3 h (13650 GHz, f = 7.02 GHz).

Ketogenic Diet in Infants with Early-Onset Epileptic Encephalopathy and SCN2A Mutation

Xiaoyu Tian,Yange Zhang,Jinhong Zhang,Yan Lu,Xinyi Men,Xiuxia Wang 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.4

Research has shown mutations in the voltage-gated sodium channel gene SCN2A to be associated with developmental delaysand infantile seizures in patients with early-onset epileptic encephalopathies (EOEEs). Here, we report the case of an infant witha de novo SCN2A mutation with EOEE who had medically refractory seizures that improved with a ketogenic diet (KD) implementedat an age less than 2 months. On the day of his birth, the infant presented with a pattern of convulsions with dozens ofepisodes per day. An initial video electroencephalogram revealed poor reactivity of background activity, with multiple partial episodesstarting from the right temporal region, and abnormal electrical activity in the right hemisphere. The seizures previouslywere not controlled with successive therapy with phenobarbital, topiramate, and levetiracetam. Genetic testing revealed the presenceof a mutation in the SCN2A gene (c.4425C>G, p.Asn1475Lys). The infant’s seizures decreased significantly with a combinationof KD and medication. The present case exemplifies the potential for personalized genomics in identifying the etiology of anillness. Furthermore, the KD appears to feasible in infants younger than 2 months and might elicit good responses to EOEE associatedwith SCN2A mutation.

Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus

Fang Ting,Liu Suyi,Chen Liying,Ren Yating,Lu Dingqi,Yao Xinyi,Hong Tao,Zhang Xvfeng,Xie Zhimin,Yang Kepeng,Wang Xinchang 한국유전학회 2023 Genes & Genomics Vol.45 No.9

Background As a multisystemic autoimmune illness, the basic mechanisms behind the pathophysiology of systemic lupus erythematosus (SLE) remain poorly understood. Objective We aimed to investigate the possible significance of SLE’s DNA methylation and gain further insight into potential SLE-related biomarkers and therapeutic targets. Methods We used whole genome bisulfite sequencing (WGBS) method to analyze DNA methylation in 4 SLE patients and 4 healthy people. Results 702 differentially methylated regions (DMRs) were identified, and 480 DMR-associated genes were annotated. We found the majority of the DMR-associated elements were enriched in repeat and gene bodies. The top 10 hub genes identified were LCK, FYB, PTK2B, LYN, CTNNB1, MAPK1, GNAQ, PRKCA, ABL1, and CD247. Compared to the control group, LCK and PTK2B had considerably decreased levels of mRNA expression in the SLE group. Receiver operating characteristic (ROC) curve suggested that LCK and PTK2B may be potential candidate biomarkers to predict SLE. Conclusions Our study improved comprehension of the DNA methylation patterns of SLE and identified potential biomarkers and therapeutic targets for SLE.

Development of Recombinase Polymerase Amplification Combined with Lateral Flow Strips for Rapid Detection of Cowpea Mild Mottle Virus

Xinyang Wu,Shuting Chen,Zixin Zhang,Yihan Zhang,Pingmei Li,Xinyi Chen,Miaomiao Liu,Qian Lu,Zhongyi Li,Zhongyan Wei,Pei Xu 한국식물병리학회 2023 Plant Pathology Journal Vol.39 No.5

Cowpea mild mottle virus (CPMMV) is a global plant virus that poses a threat to the production and quality of legume crops. Early and accurate diagnosis is essential for effective managing CPMMV outbreaks. With the advancement in isothermal recombinase polymerase amplification and lateral flow strips technologies, more rapid and sensitive methods have become available for detecting this pathogen. In this study, we have developed a reverse transcription recombinase polymerase amplification combined with lateral flow strips (RT-RPA-LFS) method for the detection of CPMMV, specifically targeting the CPMMV coat protein (CP) gene. The RT-RPA-LFS assay only requires 20 min at 40°C and demonstrates high specificity. Its detection limit was 10 copies/μl, which is approximately up to 100 times more sensitive than RT-PCR on agarose gel electrophoresis. The developed RT-RPA-LFS method offers a rapid, convenient, and sensitive approach for field detection of CPMMV, which contribute to controlling the spread of the virus.

KLF9 promotes autophagy and apoptosis in T-cell acute lymphoblastic leukemia cells by inhibiting AKT/mTOR signaling pathway

Zhao Jie,He Shaolong,Xiang Chenhuan,Zhang Shaoli,Chen Xinyue,Lu Xinyi,Yao Qiong,Yang Liping,Ma Liangming,Tian Weiwei 대한독성 유전단백체 학회 2023 Molecular & cellular toxicology Vol.19 No.3

Background T -cell acute lymphoblastic leukemia (T-ALL) is considered a malignant tumor with a high mortality rate. To combat this disease, exploring the mechanism of T-ALL progression is urgently needed. Krüppel-like factors (KLFs) are known as the transcription factors and mediate series of biological processes. KLF9 is a member of the KLF family which could serve as a tumor suppressor gene in most solid tumors. GEO Database analysis showed that KLF9 expression in normal T cells was higher than T-ALL cell lines and patients. However, the possible role of KLF9 in T-ALL progression is still unclear. Objective To uncover the possible eff ects of Krüppel-like transcription factor 9 (KLF9) on the progression of T-Acute lymphoblastic leukemia (T-ALL). Results The expression of KLF9 was low in human T-ALL cells. KLF9 suppressed the viability of T-ALL cells. In addition, KLF9 stimulated the apoptosis as well as autophagy of T-ALL cells. Mechanically, KLF9 suppressed AKT/mTOR pathway in T-ALL cells. Conclusion KLF9 suppressed viability and promoted autophagy as well as apoptosis in T-ALL cells by inhibiting AKT/ mTOR pathway.