Branchio-oto-renal(BOR)syndrome is an uncommon disorder inherited in an autosomal dominant manner.Its main clinical manifestations include branchial cleft cysts,anterior auricular fistula,hearing impairment,and kidney...Branchio-oto-renal(BOR)syndrome is an uncommon disorder inherited in an autosomal dominant manner.Its main clinical manifestations include branchial cleft cysts,anterior auricular fistula,hearing impairment,and kidney malformations.BOR syndrome is associated with heterozygous pathogenic variants including EYA1,SIX1,and SIX5.The study focused on a 13-year-old Chinese boy who presented with hearing impairment,renal malformations,and bony atresia of the right external auditory canal with microtia.The boy's clinical manifestations met the diagnostic criteria for BOR syndrome.Two of the boy's family members underwent clinical examination.However,neither displayed a phenotype associated with BOR syndrome.The boy and his two relatives provided blood samples for genomic DNA extraction,followed by Sanger sequencing.A novel mutation in the GREB1L gene was identified in the boy,but neither of his family members exhibited the same variant.Identifying a novel mutation in GREB1L offers valuable insights into the genotype-phenotype correlation of BOR syndrome,improving the precision of early diagnosis and promoting the advancement of personalized treatment strategies.展开更多
为研究银鲫(Carassius gibelio)雌激素应答基因(Growth regulation by estrogen in breast cancer cell 1,Greb1)的表达特征和功能,采用RACE方法克隆了银鲫Greb1的全长cDNA(CgGreb1)。CgGreb1的cDNA全长为954 bp,其中包含一个765 bp的...为研究银鲫(Carassius gibelio)雌激素应答基因(Growth regulation by estrogen in breast cancer cell 1,Greb1)的表达特征和功能,采用RACE方法克隆了银鲫Greb1的全长cDNA(CgGreb1)。CgGreb1的cDNA全长为954 bp,其中包含一个765 bp的开放阅读框,编码255个氨基酸。大多数脊椎动物有多个Greb1的变体,长度为386—1988个氨基酸,其中CgGreb1是最短的一个。序列比对结果表明脊椎动物Greb1蛋白的N端区域极为保守,且CgGreb1位于Greb1蛋白的N端区域,该区域与其他脊椎动物Greb1的同源性超过60%。qRT-PCR结果显示,在成体组织中,CgGreb1主要在垂体、脑、性腺和肝脏中表达,其中在垂体中CgGreb1的表达最高;在注射促黄体生成素释放激素类似物和人绒毛膜促性腺激素后的雌鱼垂体中,CgGreb1的表达逐渐上升随后降低,并在产卵时维持较高的表达;在胚胎发育过程中,CgGreb1从50%外包开始表达,其表达量随胚胎发育而升高,在受精后24h达到峰值,随后表达量下降,在受精后48h不表达。原位杂交结果表明,在原肠期,CgGreb1信号位于胚层的边缘;在体节期,CgGreb1信号逐渐增强并出现在神经系统;在受精后24h,CgGreb1信号在脑和脊髓等中枢神经系统增强;从受精后30h开始,CgGreb1信号减弱;在受精后48h,检测不到CgGreb1信号。在注射CgGreb1 MO的银鲫胚胎中,tshβ、prl和gthα分别标记的3种垂体细胞减少,证明CgGreb1参与早期银鲫垂体细胞的发育。研究结果为进一步揭示银鲫垂体发育和生长调控机制奠定了基础。展开更多
文摘Branchio-oto-renal(BOR)syndrome is an uncommon disorder inherited in an autosomal dominant manner.Its main clinical manifestations include branchial cleft cysts,anterior auricular fistula,hearing impairment,and kidney malformations.BOR syndrome is associated with heterozygous pathogenic variants including EYA1,SIX1,and SIX5.The study focused on a 13-year-old Chinese boy who presented with hearing impairment,renal malformations,and bony atresia of the right external auditory canal with microtia.The boy's clinical manifestations met the diagnostic criteria for BOR syndrome.Two of the boy's family members underwent clinical examination.However,neither displayed a phenotype associated with BOR syndrome.The boy and his two relatives provided blood samples for genomic DNA extraction,followed by Sanger sequencing.A novel mutation in the GREB1L gene was identified in the boy,but neither of his family members exhibited the same variant.Identifying a novel mutation in GREB1L offers valuable insights into the genotype-phenotype correlation of BOR syndrome,improving the precision of early diagnosis and promoting the advancement of personalized treatment strategies.
文摘为研究银鲫(Carassius gibelio)雌激素应答基因(Growth regulation by estrogen in breast cancer cell 1,Greb1)的表达特征和功能,采用RACE方法克隆了银鲫Greb1的全长cDNA(CgGreb1)。CgGreb1的cDNA全长为954 bp,其中包含一个765 bp的开放阅读框,编码255个氨基酸。大多数脊椎动物有多个Greb1的变体,长度为386—1988个氨基酸,其中CgGreb1是最短的一个。序列比对结果表明脊椎动物Greb1蛋白的N端区域极为保守,且CgGreb1位于Greb1蛋白的N端区域,该区域与其他脊椎动物Greb1的同源性超过60%。qRT-PCR结果显示,在成体组织中,CgGreb1主要在垂体、脑、性腺和肝脏中表达,其中在垂体中CgGreb1的表达最高;在注射促黄体生成素释放激素类似物和人绒毛膜促性腺激素后的雌鱼垂体中,CgGreb1的表达逐渐上升随后降低,并在产卵时维持较高的表达;在胚胎发育过程中,CgGreb1从50%外包开始表达,其表达量随胚胎发育而升高,在受精后24h达到峰值,随后表达量下降,在受精后48h不表达。原位杂交结果表明,在原肠期,CgGreb1信号位于胚层的边缘;在体节期,CgGreb1信号逐渐增强并出现在神经系统;在受精后24h,CgGreb1信号在脑和脊髓等中枢神经系统增强;从受精后30h开始,CgGreb1信号减弱;在受精后48h,检测不到CgGreb1信号。在注射CgGreb1 MO的银鲫胚胎中,tshβ、prl和gthα分别标记的3种垂体细胞减少,证明CgGreb1参与早期银鲫垂体细胞的发育。研究结果为进一步揭示银鲫垂体发育和生长调控机制奠定了基础。
