To the Editor:Tuberous sclerosis complex (TSC),with the birth incidence of 1:6000,[1] is an autosomal dominant inherited,multi-system disorder characterized by cellular hyperplasia and tissue dysplasia,among which,ren...To the Editor:Tuberous sclerosis complex (TSC),with the birth incidence of 1:6000,[1] is an autosomal dominant inherited,multi-system disorder characterized by cellular hyperplasia and tissue dysplasia,among which,renal angiomyolipoma (AML) is one common comorbidity.However,malignancy of renal AML is rare.Herein,we shared a case of malignancy of renal AML from TSC in a young man.展开更多
Objective To study the relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex(TSC).Methods The clinical data of76 patients with TSC diagnosed in Guangdong 999 Brain Hospi...Objective To study the relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex(TSC).Methods The clinical data of76 patients with TSC diagnosed in Guangdong 999 Brain Hospital were collected between May 2007 and 2014 and then TSC gene mutation analysis was performed.Genotype-phenotype analyses for all the patients were also carried out.Results Fifty of the 76(66%)patients展开更多
Tuberous sclerosis complex （TSC） is a relatively common autosomal dominant genetic disorder affecting l/14,000-1/6000 Western populations.The incidence of TSC in Chinese population is still unknown although case rep...Tuberous sclerosis complex （TSC） is a relatively common autosomal dominant genetic disorder affecting l/14,000-1/6000 Western populations.The incidence of TSC in Chinese population is still unknown although case reports of Chinese TSC patients were documented. The main clinical features of TSC include seizures,mental retardation,and the development ofhamartomas in multiple organs such as the skin,brain,lung,heart,and kidney.Indeed,the disease virtually manifests in every organ. Two causative genes for TSC,TSC 1 gene on chromosome 9q34 and TSC2 gene on chromosome16p13,have been identified in 1997 and 1993 respectively.Approximately,70% of cases of TSC are de novo mutations. Chinese TSC patients are more likely to have TSC2 missense and frame shift mutations.Here,we record one Chinese TSC family and it is novel frame shift mutation of TSC2.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
Tuberous sclerosis complex(TSC) is a neurocutaneous syndrome with serious clinical presentations, an autosomal dominant genetic disorder involving multiple organs and systems. We retrospectively investigated the clini...Tuberous sclerosis complex(TSC) is a neurocutaneous syndrome with serious clinical presentations, an autosomal dominant genetic disorder involving multiple organs and systems. We retrospectively investigated the clinical manifestations and genotypes of 20 Chinese children with TSC to enable informed diagnostic and surveillance recommendations in China. A retrospective analysis of clinical manifestations in 20 children(7.00±5.30 years old) with TSC was conducted. A genetic testing of the genes TSC1 and TSC2 was performed in 14 children.The earliest manifestations of TSC were skin lesions(80% of patients) and seizures(75%). Fourteen of the children presented with retinal hamartomas, and 2 of these underwent eye enucleation at other hospitals through misdiagnosis. On magnetic resonance imaging, 18 children exhibited subependymal nodules, and 16 ones showed cortical nodules. 5 cases of non-renal hamartomas, 5 cases of multiple renal cysts, and 5 cases of cardiac rhabdomyomas were observed.The genotyping of TSC1 and TSC2 in 14 children revealed 11 with mutations in TSC2, 2 with mutations in TSC1, and no mutations of either gene in one patient. Eight of these observed mutations are reported here in for the first time. The illness presentations of the TSC2-mutated patients were more severe than that of patients carrying TSC1 mutations.There were differences in the mutations of TSC genes in Chinese children from those reported in other countries. The described clinical characteristics and genotyping will help pediatric neurologists to understand, diagnosis, and treat TSC.展开更多
目的:研究2例中国汉族人结节性硬化症TSC1和TSC2基因的突变情况。方法:采用聚合酶链反应扩增2例结节性硬化症患者、患者家族中的正常人及100名健康对照者的TSC1和TSC2基因的全部外显子,并进行DNA测序分析。结果:家系I发现一个无义突变(n...目的:研究2例中国汉族人结节性硬化症TSC1和TSC2基因的突变情况。方法:采用聚合酶链反应扩增2例结节性硬化症患者、患者家族中的正常人及100名健康对照者的TSC1和TSC2基因的全部外显子,并进行DNA测序分析。结果:家系I发现一个无义突变(nonsense mutation):TSC2基因第1372位碱基由胞嘧啶(C)突变为胸腺嘧啶(T),导致第458位氨基酸(精氨酸)处提前出现终止密码子。散发患者II发生了一处移码突变(frame shift mutation):TSC2基因第5238位与5255位碱基之间缺失CATCAAGCGGCTCCGCCA18个碱基,其后密码子发生移位。结论:无义突变c.1372C>T(p.R458X)和移码突变5238-5255 del 18 bp CATCAAGCGGCTCCGCCA1746 del HIKRLR可能是导致这2例患者临床发病的主要原因。展开更多
文摘To the Editor:Tuberous sclerosis complex (TSC),with the birth incidence of 1:6000,[1] is an autosomal dominant inherited,multi-system disorder characterized by cellular hyperplasia and tissue dysplasia,among which,renal angiomyolipoma (AML) is one common comorbidity.However,malignancy of renal AML is rare.Herein,we shared a case of malignancy of renal AML from TSC in a young man.
文摘目的检测并分析2例中国汉族结节性硬化症(tuberous sclerosis complex,TSC)患者TSC2基因突变特点。方法采用直接测序法对31个家系的34例TSC患者及其父母33名进行TSC1基因和TSC2基因全长编码外显子基因检测。测序后发现第25家系先证者为TSC2基因外显子40的框内移码突变5238-5255 del 18 bp,第11家系先证者为TSC2基因外显子23错义突变Arg905Trp。进一步采用变性凝胶电泳及内切酶技术在患者与120名正常对照中检测这两种突变。结果第25家系先证者外显子40出现5238-5255d el CATCAAGCGGCTCCGCCA突变,导致6个氨基酸缺失的框内移码突变(1746-1751del His-Ile-Lys-Arg-Leu-Gly),第11家系先证者外显子23出现2713 C>T(Arg905Trp)错义突变,2713位碱基由胞嘧啶(C)改变为胸腺嘧啶(T),导致第905位氨基酸精氨酸被色氨酸替代。120名正常对照未检测到这两种突变。结论TSC2基因5238-5255 del 18 bp及2713 C>T突变为两种致病性突变。
文摘Objective To study the relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex(TSC).Methods The clinical data of76 patients with TSC diagnosed in Guangdong 999 Brain Hospital were collected between May 2007 and 2014 and then TSC gene mutation analysis was performed.Genotype-phenotype analyses for all the patients were also carried out.Results Fifty of the 76(66%)patients
文摘Tuberous sclerosis complex （TSC） is a relatively common autosomal dominant genetic disorder affecting l/14,000-1/6000 Western populations.The incidence of TSC in Chinese population is still unknown although case reports of Chinese TSC patients were documented. The main clinical features of TSC include seizures,mental retardation,and the development ofhamartomas in multiple organs such as the skin,brain,lung,heart,and kidney.Indeed,the disease virtually manifests in every organ. Two causative genes for TSC,TSC 1 gene on chromosome 9q34 and TSC2 gene on chromosome16p13,have been identified in 1997 and 1993 respectively.Approximately,70% of cases of TSC are de novo mutations. Chinese TSC patients are more likely to have TSC2 missense and frame shift mutations.Here,we record one Chinese TSC family and it is novel frame shift mutation of TSC2.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
基金supported by the Capital Health Research and Development of Special (2014-1-4091)
文摘Tuberous sclerosis complex(TSC) is a neurocutaneous syndrome with serious clinical presentations, an autosomal dominant genetic disorder involving multiple organs and systems. We retrospectively investigated the clinical manifestations and genotypes of 20 Chinese children with TSC to enable informed diagnostic and surveillance recommendations in China. A retrospective analysis of clinical manifestations in 20 children(7.00±5.30 years old) with TSC was conducted. A genetic testing of the genes TSC1 and TSC2 was performed in 14 children.The earliest manifestations of TSC were skin lesions(80% of patients) and seizures(75%). Fourteen of the children presented with retinal hamartomas, and 2 of these underwent eye enucleation at other hospitals through misdiagnosis. On magnetic resonance imaging, 18 children exhibited subependymal nodules, and 16 ones showed cortical nodules. 5 cases of non-renal hamartomas, 5 cases of multiple renal cysts, and 5 cases of cardiac rhabdomyomas were observed.The genotyping of TSC1 and TSC2 in 14 children revealed 11 with mutations in TSC2, 2 with mutations in TSC1, and no mutations of either gene in one patient. Eight of these observed mutations are reported here in for the first time. The illness presentations of the TSC2-mutated patients were more severe than that of patients carrying TSC1 mutations.There were differences in the mutations of TSC genes in Chinese children from those reported in other countries. The described clinical characteristics and genotyping will help pediatric neurologists to understand, diagnosis, and treat TSC.
文摘目的:研究2例中国汉族人结节性硬化症TSC1和TSC2基因的突变情况。方法:采用聚合酶链反应扩增2例结节性硬化症患者、患者家族中的正常人及100名健康对照者的TSC1和TSC2基因的全部外显子,并进行DNA测序分析。结果:家系I发现一个无义突变(nonsense mutation):TSC2基因第1372位碱基由胞嘧啶(C)突变为胸腺嘧啶(T),导致第458位氨基酸(精氨酸)处提前出现终止密码子。散发患者II发生了一处移码突变(frame shift mutation):TSC2基因第5238位与5255位碱基之间缺失CATCAAGCGGCTCCGCCA18个碱基,其后密码子发生移位。结论:无义突变c.1372C>T(p.R458X)和移码突变5238-5255 del 18 bp CATCAAGCGGCTCCGCCA1746 del HIKRLR可能是导致这2例患者临床发病的主要原因。
