AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was i...AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.展开更多
Background:Osteosarcoma is the most common primary bone malignancy,with a strong tendency towards local invasion and metastasis.The SRY-Box Transcription Factor 1(SOX1)gene,a member of the HMG-box family of DNA-bindin...Background:Osteosarcoma is the most common primary bone malignancy,with a strong tendency towards local invasion and metastasis.The SRY-Box Transcription Factor 1(SOX1)gene,a member of the HMG-box family of DNA-binding transcription factors,plays a crucial role in embryogenesis and tumorigenesis.However,its role in osteosarcoma,particularly in relation to metastatic potential,is not well understood.Methods:The GSE14359 dataset containing five samples of conventional osteosarcoma and four samples of lung metastatic osteosarcoma was obtained from the Gene Expression Omnibus(GEO)database and analyzed for differential gene expression using the R language.Gene expression was detected using qPCR and Western blotting.Transcriptional activity was assessed by Luciferase reporter gene assays,and cell metastatic ability was assessed by migration and invasion assays.Results:The study demonstrated that SOX1 binds to a specific response element within the Transmembrane 4 Superfamily Member 12(TSPAN12)promoter,upregulating TSPAN12 and its associated inflammatory pathways.Silencing TSPAN12 markedly reduces SOX1-mediated osteosarcoma cell invasion and inflammatory response,while TSPAN12 overexpression reverses these effects in SOX1-suppressed cells.Conclusion:In this study,our findings elucidate SOX1’s role in enhancing osteosarcoma metastasis via TSPAN12 upregulation,offering new insights into the molecular mechanisms of osteosarcoma progression.展开更多
基金Supported by the National Natural Science Foundation of China(No.82060183)Ningxia Natural Science Foundation(No.2022AAC03388)the Key Research and Development Project of Ningxia Hui Autonomous Region(No.2021BEG02045,No.2020BEG03044).
文摘AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
文摘Background:Osteosarcoma is the most common primary bone malignancy,with a strong tendency towards local invasion and metastasis.The SRY-Box Transcription Factor 1(SOX1)gene,a member of the HMG-box family of DNA-binding transcription factors,plays a crucial role in embryogenesis and tumorigenesis.However,its role in osteosarcoma,particularly in relation to metastatic potential,is not well understood.Methods:The GSE14359 dataset containing five samples of conventional osteosarcoma and four samples of lung metastatic osteosarcoma was obtained from the Gene Expression Omnibus(GEO)database and analyzed for differential gene expression using the R language.Gene expression was detected using qPCR and Western blotting.Transcriptional activity was assessed by Luciferase reporter gene assays,and cell metastatic ability was assessed by migration and invasion assays.Results:The study demonstrated that SOX1 binds to a specific response element within the Transmembrane 4 Superfamily Member 12(TSPAN12)promoter,upregulating TSPAN12 and its associated inflammatory pathways.Silencing TSPAN12 markedly reduces SOX1-mediated osteosarcoma cell invasion and inflammatory response,while TSPAN12 overexpression reverses these effects in SOX1-suppressed cells.Conclusion:In this study,our findings elucidate SOX1’s role in enhancing osteosarcoma metastasis via TSPAN12 upregulation,offering new insights into the molecular mechanisms of osteosarcoma progression.
