探究沉默溶质载体家-2促进葡萄糖转运蛋白成员-1(solute carrier family 2 member 1, SLC2A1)基因对肺腺癌细胞恶性进展的影响。方法 从肿瘤与癌症基因组图谱(The cancer genome atlas,TCGA)数据库中下载SLC2A1在人正常肺组织和肺腺癌...探究沉默溶质载体家-2促进葡萄糖转运蛋白成员-1(solute carrier family 2 member 1, SLC2A1)基因对肺腺癌细胞恶性进展的影响。方法 从肿瘤与癌症基因组图谱(The cancer genome atlas,TCGA)数据库中下载SLC2A1在人正常肺组织和肺腺癌组织中的表达谱数据。通过qRT-PCR、 western blot等方法分析SLC2A1在肺腺癌发生发展中的作用。CCK8法测定肿瘤细胞的生长活性, Transwell法测定肿瘤细胞的迁移与浸润, FCM法测定肿瘤细胞的凋亡。结果 从535名肺癌病人及59名健康人标本中,发现SLC2A1的表达量明显升高。我们前期研究发现,SLC2A1基因敲除后,可明显降低肺癌细胞的增殖、迁移和侵袭能力,并诱导其凋亡(P<0.05)。结论 SLC2A1基因在肺腺癌细胞系及临床标本中均呈高表达,其基因敲除后,可明显降低肺癌细胞的增殖、迁移及侵袭能力,并诱导肺癌细胞的凋亡。展开更多
Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome.Methods ...Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome.Methods Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing.We analyzed the patients’convulsions and treatment with antiepileptic drugs.The patients were followed up at different time periods after ketogenic diet therapies.Results Six patients with SLC2A1 mutations were included in this study.The patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their symptoms.They were then treated with a ketogenic diet for at least four months.We analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet treatment.All patients were seizure-free within a month of receiving the diet therapy.All patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this period.After antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone.No severe adverse events occurred during the therapy.Conclusions Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations.Therefore,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.展开更多
Background The SLC2A1 gene plays a vital role in brain energy metabolism.SLC2A1 variants have been reported to be associated with early-onset refractory seizures.This study aims to explore the association between the ...Background The SLC2A1 gene plays a vital role in brain energy metabolism.SLC2A1 variants have been reported to be associated with early-onset refractory seizures.This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy.Methods Trios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies.The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results A total of 14 heterozygous SLC2A1 variants were identifed in 16 unrelated families.The variants were evaluated as“pathogenic”or“likely pathogenic”according to the ACMG guidelines.Ten cases(62.5%)presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy(DEE).The other six cases(37.5%)exhibited late-onset seizures and normal development.They were diagnosed with idiopathic partial epilepsy(n=2)or idiopathic generalized epilepsy(n=4).Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region,whereas the mild epilepsyassociated variants tended to locate in regions outside the transmembrane region,suggesting a potential molecular sub-regional efect.A total of 15 cases had delayed diagnosis,with the longest delay being 22 years.The SLC2A1 expression stage,which is expressed at relatively high level throughout the whole life span,from the embryonic to adult stages with two peaks at approximately four and 14 years,is generally consistent with the seizure onset age.In addition,patients with early-onset age had variants that were potentially associated with severe damage,suggesting a potential correlation between the age of disease onset and the damaging efects of the variants.Conclusions SLC2A1 variants are associated with late-onset epilepsy,which is consistent with the genetic-dependent stage feature of SLC2A1.Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.展开更多
文摘探究沉默溶质载体家-2促进葡萄糖转运蛋白成员-1(solute carrier family 2 member 1, SLC2A1)基因对肺腺癌细胞恶性进展的影响。方法 从肿瘤与癌症基因组图谱(The cancer genome atlas,TCGA)数据库中下载SLC2A1在人正常肺组织和肺腺癌组织中的表达谱数据。通过qRT-PCR、 western blot等方法分析SLC2A1在肺腺癌发生发展中的作用。CCK8法测定肿瘤细胞的生长活性, Transwell法测定肿瘤细胞的迁移与浸润, FCM法测定肿瘤细胞的凋亡。结果 从535名肺癌病人及59名健康人标本中,发现SLC2A1的表达量明显升高。我们前期研究发现,SLC2A1基因敲除后,可明显降低肺癌细胞的增殖、迁移和侵袭能力,并诱导其凋亡(P<0.05)。结论 SLC2A1基因在肺腺癌细胞系及临床标本中均呈高表达,其基因敲除后,可明显降低肺癌细胞的增殖、迁移及侵袭能力,并诱导肺癌细胞的凋亡。
基金supported by grants from National Key R&D Program of China(2019YFA0801900)Epilepsy Research Fund of China Association Against Epilepsy(CJ-B-2021-21)+5 种基金The Interdisciplinary Program of Shanghai Jiao Tong University(YG2021QN108)Emerging Frontier Technology Project of Shanghai Hospital(SHDC12015113)Research Funds of Shanghai Health and Family Planning Commission(20204Y0339)Shanghai Hospital Development Center Foundation(SHDC12022626,SHDC2022CRS052)Shanghai“Rising Stars of Medical Talent”Youth Development Program-Youth Medical Talents-Clinical Pharmacist Program(SHWRS(2020)_087)Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20212800).
文摘Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome.Methods Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing.We analyzed the patients’convulsions and treatment with antiepileptic drugs.The patients were followed up at different time periods after ketogenic diet therapies.Results Six patients with SLC2A1 mutations were included in this study.The patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their symptoms.They were then treated with a ketogenic diet for at least four months.We analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet treatment.All patients were seizure-free within a month of receiving the diet therapy.All patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this period.After antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone.No severe adverse events occurred during the therapy.Conclusions Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations.Therefore,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.
基金supported by the National Natural Science Foundation of China(82271505 to W.L.)UCB Pharma Ltd.and the Joint Science Research Foundation of China Association Against Epilepsy(CU-2024-042 to B.L.).
文摘Background The SLC2A1 gene plays a vital role in brain energy metabolism.SLC2A1 variants have been reported to be associated with early-onset refractory seizures.This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy.Methods Trios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies.The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics(ACMG)guidelines.Results A total of 14 heterozygous SLC2A1 variants were identifed in 16 unrelated families.The variants were evaluated as“pathogenic”or“likely pathogenic”according to the ACMG guidelines.Ten cases(62.5%)presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy(DEE).The other six cases(37.5%)exhibited late-onset seizures and normal development.They were diagnosed with idiopathic partial epilepsy(n=2)or idiopathic generalized epilepsy(n=4).Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region,whereas the mild epilepsyassociated variants tended to locate in regions outside the transmembrane region,suggesting a potential molecular sub-regional efect.A total of 15 cases had delayed diagnosis,with the longest delay being 22 years.The SLC2A1 expression stage,which is expressed at relatively high level throughout the whole life span,from the embryonic to adult stages with two peaks at approximately four and 14 years,is generally consistent with the seizure onset age.In addition,patients with early-onset age had variants that were potentially associated with severe damage,suggesting a potential correlation between the age of disease onset and the damaging efects of the variants.Conclusions SLC2A1 variants are associated with late-onset epilepsy,which is consistent with the genetic-dependent stage feature of SLC2A1.Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.
