CSMD1基因(CUB and Sushimultiple domains1)是2001年新发现的候选抑癌基因,定位于人染色体8p23.2,其编码蛋白质包括14个CUB和28个Sushi结构域,是一种跨膜蛋白。已证实CSMD1基因在多种组织中有表达,并且该基因的表达缺失或功能异常与多...CSMD1基因(CUB and Sushimultiple domains1)是2001年新发现的候选抑癌基因,定位于人染色体8p23.2,其编码蛋白质包括14个CUB和28个Sushi结构域,是一种跨膜蛋白。已证实CSMD1基因在多种组织中有表达,并且该基因的表达缺失或功能异常与多种肿瘤的发生有着密切的联系。目前,CSMD1基因与头颈部肿瘤的关系成为人们关注的焦点,有研究表明该基因是头颈部鳞癌的抑制基因,但由于缺乏足够的证据,尚存在着争议。展开更多
CSMD1(CUB and SUSHI multiple domains-1)位于人染色体8p23.2,是一种单次跨膜蛋白,由14个CUB和28个SUSHI结构域组成。该基因的表达缺失或功能异常与多种肿瘤的发生发展有着密切的关系。目前,在肝细胞肝癌(hepatocellular carcinoma,HCC...CSMD1(CUB and SUSHI multiple domains-1)位于人染色体8p23.2,是一种单次跨膜蛋白,由14个CUB和28个SUSHI结构域组成。该基因的表达缺失或功能异常与多种肿瘤的发生发展有着密切的关系。目前,在肝细胞肝癌(hepatocellular carcinoma,HCC)中也发现了CSMD1的杂合性丢失(loss of heterozygosity,LOH),但其作用机制尚不明确。作为一种新的候选抑癌基因,CSMD1的研究有待于进一步深入。展开更多
精神分裂症是一种严重的精神疾病,大多数患者伴有认知功能的缺陷,给患者、家庭和社会造成了相当大的负担。精神分裂症的遗传率较高。在过去的十年中,发现许多与精神分裂症有关的基因变异,从而使人们更好地理解其遗传结构的复杂性。最近...精神分裂症是一种严重的精神疾病,大多数患者伴有认知功能的缺陷,给患者、家庭和社会造成了相当大的负担。精神分裂症的遗传率较高。在过去的十年中,发现许多与精神分裂症有关的基因变异,从而使人们更好地理解其遗传结构的复杂性。最近的研究还表明,部分与精神分裂症有关的基因变异会影响认知能力。进一步研究这些基因对认知功能的影响将有助于了解遗传因素对精神分裂症认知功能障碍的作用。本综述旨在探讨CSMD1(CUB and SUSHI multiple domains-1)基因多态性与精神分裂症及其认知功能损害关系的研究进展。展开更多
Genetic factors are the major causes of epilepsies,such as developmental and epileptic encephalopathy(DEE)and idiopathic generalized epilepsy(IGE).However,the etiology of most patients remains elusive.This study perfo...Genetic factors are the major causes of epilepsies,such as developmental and epileptic encephalopathy(DEE)and idiopathic generalized epilepsy(IGE).However,the etiology of most patients remains elusive.This study performed exon sequencing in a cohort of 173 pa-tients with IGE.Additional cases were recruited from the matching platform in China.The excess and damaging effect of variants,the genotype-phenotype correlation,and the correlation be-tween gene expression and phenotype were studied to validate the geneedisease association.CSMD1 compound heterozygous variants were identified in four unrelated cases with IGE.Addi-tional CSMD1 variants were identified in five cases with DEE featured by generalized seizures from the matching platform,including two with de novo and three with compound heterozygous variants.Two patients were refractory to antiseizure medications and all patients were on long-term therapy.The CSMD1 variants presented a significantly high excess of variants in the case-cohort.Besides de novo origination,the DEE cases had each of the paired variants located closer to each other than the IGE cases or more significant alterations in hydrophobicity.The DEE-asso-ciated variants were all absent in the normal population and presented significantly lower minor allele frequency than the IGE-associated variants,suggesting a minor allele frequency-pheno-type severity correlation.Gene expression analysis showed that CSMD1 was extensively ex-pressed throughout the brain,particularly in the cortex.The CSMD1 temporal expression pattern correlated with the disease onset and outcomes.This study suggests that CSMD1 is asso-ciated with epilepsy and is a novel causative gene of DEE and generalized epilepsies.展开更多
文摘CSMD1基因(CUB and Sushimultiple domains1)是2001年新发现的候选抑癌基因,定位于人染色体8p23.2,其编码蛋白质包括14个CUB和28个Sushi结构域,是一种跨膜蛋白。已证实CSMD1基因在多种组织中有表达,并且该基因的表达缺失或功能异常与多种肿瘤的发生有着密切的联系。目前,CSMD1基因与头颈部肿瘤的关系成为人们关注的焦点,有研究表明该基因是头颈部鳞癌的抑制基因,但由于缺乏足够的证据,尚存在着争议。
文摘CSMD1(CUB and SUSHI multiple domains-1)位于人染色体8p23.2,是一种单次跨膜蛋白,由14个CUB和28个SUSHI结构域组成。该基因的表达缺失或功能异常与多种肿瘤的发生发展有着密切的关系。目前,在肝细胞肝癌(hepatocellular carcinoma,HCC)中也发现了CSMD1的杂合性丢失(loss of heterozygosity,LOH),但其作用机制尚不明确。作为一种新的候选抑癌基因,CSMD1的研究有待于进一步深入。
文摘精神分裂症是一种严重的精神疾病,大多数患者伴有认知功能的缺陷,给患者、家庭和社会造成了相当大的负担。精神分裂症的遗传率较高。在过去的十年中,发现许多与精神分裂症有关的基因变异,从而使人们更好地理解其遗传结构的复杂性。最近的研究还表明,部分与精神分裂症有关的基因变异会影响认知能力。进一步研究这些基因对认知功能的影响将有助于了解遗传因素对精神分裂症认知功能障碍的作用。本综述旨在探讨CSMD1(CUB and SUSHI multiple domains-1)基因多态性与精神分裂症及其认知功能损害关系的研究进展。
基金supported by the National Natural Science Foundation of China(No.82271505 to W.P.L.)the Multi-center Clinical Research Fund Project of the Second Affiliated Hospital of Guangzhou Medical University(No.010G271099,2020-LCYJ-DZX-03 to W.P.L.)the Science and Technology Project of Guangzhou,Guangdong,China(No.201904020028 to W.P.L.).
文摘Genetic factors are the major causes of epilepsies,such as developmental and epileptic encephalopathy(DEE)and idiopathic generalized epilepsy(IGE).However,the etiology of most patients remains elusive.This study performed exon sequencing in a cohort of 173 pa-tients with IGE.Additional cases were recruited from the matching platform in China.The excess and damaging effect of variants,the genotype-phenotype correlation,and the correlation be-tween gene expression and phenotype were studied to validate the geneedisease association.CSMD1 compound heterozygous variants were identified in four unrelated cases with IGE.Addi-tional CSMD1 variants were identified in five cases with DEE featured by generalized seizures from the matching platform,including two with de novo and three with compound heterozygous variants.Two patients were refractory to antiseizure medications and all patients were on long-term therapy.The CSMD1 variants presented a significantly high excess of variants in the case-cohort.Besides de novo origination,the DEE cases had each of the paired variants located closer to each other than the IGE cases or more significant alterations in hydrophobicity.The DEE-asso-ciated variants were all absent in the normal population and presented significantly lower minor allele frequency than the IGE-associated variants,suggesting a minor allele frequency-pheno-type severity correlation.Gene expression analysis showed that CSMD1 was extensively ex-pressed throughout the brain,particularly in the cortex.The CSMD1 temporal expression pattern correlated with the disease onset and outcomes.This study suggests that CSMD1 is asso-ciated with epilepsy and is a novel causative gene of DEE and generalized epilepsies.
