Background： Paroxysmal kinesigenic dyskinesia （PKD） is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutatio...Background： Paroxysmal kinesigenic dyskinesia （PKD） is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap. Methods： A cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited, Clinical features were evaluated, and all subjects were screened for MR-l, SLC2A1, and CLCN1 genes, which are the causative genes of paroxysmal nonkinesigenic dyskinesia （PNKD）, paroxysmal exertion-induced dyskinesia, and myotonia congenita （MC）, respectively, In addition, 200 genetically matched healthy individuals were recruited as controls. Results： A total of 16 genetic variants including 4 in MR-1 gene, 8 in SLC2A1 gene, and 4 in CLCN1 gene were detected. Among them, SLC2A1 c.363G〉A mutation was detected in one case, and CLCN1 c. 1205C〉T mutation was detected in other two cases. Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database. Both mutations were predicted to be pathogenic by SIFT and PolyPhen2. The SLC2A 1 c.363G〉A mutation was novel. Conclusions： The phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC. For those PRRT2-negative PKD cases, screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.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
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
基金Supplementary information is linked to the online version of the paper on the Chinese Medical Journal website.This work was supported by grants from the National Natural Science Foundation of China to Zhi-Ying Wu （No. 81330025 and No. 81125009）.
文摘Background： Paroxysmal kinesigenic dyskinesia （PKD） is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap. Methods： A cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited, Clinical features were evaluated, and all subjects were screened for MR-l, SLC2A1, and CLCN1 genes, which are the causative genes of paroxysmal nonkinesigenic dyskinesia （PNKD）, paroxysmal exertion-induced dyskinesia, and myotonia congenita （MC）, respectively, In addition, 200 genetically matched healthy individuals were recruited as controls. Results： A total of 16 genetic variants including 4 in MR-1 gene, 8 in SLC2A1 gene, and 4 in CLCN1 gene were detected. Among them, SLC2A1 c.363G〉A mutation was detected in one case, and CLCN1 c. 1205C〉T mutation was detected in other two cases. Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database. Both mutations were predicted to be pathogenic by SIFT and PolyPhen2. The SLC2A 1 c.363G〉A mutation was novel. Conclusions： The phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC. For those PRRT2-negative PKD cases, screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.
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.
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。
