目的分析1例Perlman综合征患儿的临床表型及DIS3L2基因变异,了解其可能的致病原因。方法抽取患儿及其父母外周血,对患儿进行全外显子测序分析,根据筛出致病基因变异对患儿及其父母进行Sanger测序验证。按照美国医学遗传学与基因组学学会...目的分析1例Perlman综合征患儿的临床表型及DIS3L2基因变异,了解其可能的致病原因。方法抽取患儿及其父母外周血,对患儿进行全外显子测序分析,根据筛出致病基因变异对患儿及其父母进行Sanger测序验证。按照美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)的基因变异解读标准与指南对基因变异进行致病性评估。结果全外显子测序结果显示患儿DIS3L2基因存在c.2109delC和c.1829-1830insC变异,Sanger测序结果显示患儿DIS3L2基因存在c.2109delC和c.1829-1830insC复合杂合变异,父亲携带DIS3L2基因c.1829-c.1830insC杂合变异,母亲携带DIS3L2基因c.2109delC杂合变异;这2个变异均为未报道过的新变异(noval),根据ACMG变异标准与指南,均判定为致病性变异(PVS1+PS2+PM2)。结论DIS3L2基因c.2109delC和c.1829-1830insC复合杂合变异可能是导致患儿临床表现的原因,新变异的检出丰富了DIS3L2基因变异谱。展开更多
Regeneration,relying mainly on resident adult stem cells,is widespread.However,the mechanism by which stem cells initiate proliferation during this process in vivo is unclear.Using planarian as a model,we screened 46 ...Regeneration,relying mainly on resident adult stem cells,is widespread.However,the mechanism by which stem cells initiate proliferation during this process in vivo is unclear.Using planarian as a model,we screened 46 transcripts showing potential function in the regulation of local stem cell proliferation following 48 h regeneration.By analyzing the regeneration defects and the mitotic activity of animals under administration of RNA interference(RNAi),we identified factor for initiating regeneration 1(Fir1)required for local proliferation.Our findings reveal that Fir1,enriched in neoblasts,promotes planarian regeneration in any tissue-missing context.Further,we demonstrate that DIS3 like 3-5'exoribonuclease 2(Dis3l2)is required for Fir1 phenotype.Besides,RNAi knockdown of Fir1 causes a decrease of neoblast wound response genes following amputation.These findings suggest that Fir1 recognizes regenerative signals and promotes DIS3L2 proteins to trigger neoblast proliferation following amputation and provide a mechanism critical for stem cell response to injury.展开更多
文摘目的分析1例Perlman综合征患儿的临床表型及DIS3L2基因变异,了解其可能的致病原因。方法抽取患儿及其父母外周血,对患儿进行全外显子测序分析,根据筛出致病基因变异对患儿及其父母进行Sanger测序验证。按照美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)的基因变异解读标准与指南对基因变异进行致病性评估。结果全外显子测序结果显示患儿DIS3L2基因存在c.2109delC和c.1829-1830insC变异,Sanger测序结果显示患儿DIS3L2基因存在c.2109delC和c.1829-1830insC复合杂合变异,父亲携带DIS3L2基因c.1829-c.1830insC杂合变异,母亲携带DIS3L2基因c.2109delC杂合变异;这2个变异均为未报道过的新变异(noval),根据ACMG变异标准与指南,均判定为致病性变异(PVS1+PS2+PM2)。结论DIS3L2基因c.2109delC和c.1829-1830insC复合杂合变异可能是导致患儿临床表现的原因,新变异的检出丰富了DIS3L2基因变异谱。
基金the National Key Research and Development Program of China(2017YFA0103700)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020903)the National Natural Science Foundation of China(91739301,91339205,and 31229002).
文摘Regeneration,relying mainly on resident adult stem cells,is widespread.However,the mechanism by which stem cells initiate proliferation during this process in vivo is unclear.Using planarian as a model,we screened 46 transcripts showing potential function in the regulation of local stem cell proliferation following 48 h regeneration.By analyzing the regeneration defects and the mitotic activity of animals under administration of RNA interference(RNAi),we identified factor for initiating regeneration 1(Fir1)required for local proliferation.Our findings reveal that Fir1,enriched in neoblasts,promotes planarian regeneration in any tissue-missing context.Further,we demonstrate that DIS3 like 3-5'exoribonuclease 2(Dis3l2)is required for Fir1 phenotype.Besides,RNAi knockdown of Fir1 causes a decrease of neoblast wound response genes following amputation.These findings suggest that Fir1 recognizes regenerative signals and promotes DIS3L2 proteins to trigger neoblast proliferation following amputation and provide a mechanism critical for stem cell response to injury.
