目的分析XY女性性逆转患者核受体亚家族5,组A,成员1(nuclear receptor subfamily 5 group A member 1,NR5A1)基因的基因突变情况。方法抽提样本外周血白细胞的DNA,对NR5A1的2~7外显子进行PCR扩增,扩增产物直接测序,重复实验和克隆测序...目的分析XY女性性逆转患者核受体亚家族5,组A,成员1(nuclear receptor subfamily 5 group A member 1,NR5A1)基因的基因突变情况。方法抽提样本外周血白细胞的DNA,对NR5A1的2~7外显子进行PCR扩增,扩增产物直接测序,重复实验和克隆测序实验验证检测到的突变,酶切分析筛查110名正常人群排除突变的多态性。结果在5例样本中未检出明显异常的突变,只在样本4中检出1个多态突变(p.G146A),该突变在正常对照人群中检出了37.3%的突变率。结论尽管在本研究中只检出1个基因多态突变,但结合国外报道,NR5A1的基因突变和性逆转的发生还是存在相关性。展开更多
This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development(DSD)patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1(NR...This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development(DSD)patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1(NR5A1)gene.Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1.The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development.The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis.Microfluidic-based single-cell RNA sequencing(scRNA-seq)analysis found that the fibroblast cells were significantly increased(approximately 46.5%),whereas the number of main epididymal epithelial cells(approximately 9.2%),such as principal cells and basal cells,was dramatically decreased.Bioinformatics analysis of cell–cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition(EMT)process.The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.展开更多
目的探讨1例46,XY性发育异常(disorders of sex development,DSD)患儿的遗传学机制,并分析其基因型与表型的相关性。方法对患儿进行全外显子组测序,并对其NR5A1基因的第1~7外显子进行多重连接探针扩增检测。结果患儿表现为幼稚女童外阴,...目的探讨1例46,XY性发育异常(disorders of sex development,DSD)患儿的遗传学机制,并分析其基因型与表型的相关性。方法对患儿进行全外显子组测序,并对其NR5A1基因的第1~7外显子进行多重连接探针扩增检测。结果患儿表现为幼稚女童外阴,Tanner分期为1期。B超可见卵巢和子宫。患儿外周血染色体核型为46,XY,全外显子组测序发现其携带NR5A1基因第5外显子杂合缺失(chr9q33.3:127255298-127255438),为新发现的致病变异,遗传自母亲,父亲未见异常。结论46,XY DSD患儿主要表现为外生殖器男性化不足,NR5A1基因变异是其重要的遗传学病因。全外显子组测序提高了基因变异的检出率,为患儿家庭的遗传咨询提供了确切的依据。展开更多
目的探究46,XY女性性逆转患者与核受体亚家族5组A成员1(nuclear receptor subfamily 5 group A member 1,NR5A1)基因突变的相关性。方法通过染色体核型分析选取符合条件的样本,提取外周血全基因组DNA,对NR5A1基因的6个(2~7)外显子进行PC...目的探究46,XY女性性逆转患者与核受体亚家族5组A成员1(nuclear receptor subfamily 5 group A member 1,NR5A1)基因突变的相关性。方法通过染色体核型分析选取符合条件的样本,提取外周血全基因组DNA,对NR5A1基因的6个(2~7)外显子进行PCR扩增,所得产物经过电泳后直接测序,并进行重复实验验证检测到的突变,同时以102名正常人群作为对照组,排除基因多态性的影响。结果在7例样本中未检出新的突变,在样本1,4,5中检出1个多态突变(p.G146A),该突变在正常对照人群中检出了43.14%的突变率;在样本1和3的5号外显子中发现Q314Q(C.942G>A,rs201103618),在样本2的4号外显子发现了P130P(C.390G>C),在其他外显子中没有发现突变。结论分析本研究的实验结果并结合国内外的相关资料报道,在四川地区,NR5A1基因突变和46,XY女性性逆转的发生可能存在相关性,进一步的深入研究是有必要的。展开更多
NR5A1基因突变是46,XY性发育异常(46,XY disorder of sex development,46,XYDSD)常见的病因之一,为常染色体显性遗传病,其临床表型多样。46,XY性腺发育不良是最常见的临床表现,特定位点突变的患儿可出现肾上腺功能不良,一些患儿的身高...NR5A1基因突变是46,XY性发育异常(46,XY disorder of sex development,46,XYDSD)常见的病因之一,为常染色体显性遗传病,其临床表型多样。46,XY性腺发育不良是最常见的临床表现,特定位点突变的患儿可出现肾上腺功能不良,一些患儿的身高可受影响。近年来越来越多的研究证明,NR5A1基因突变可以导致46,XX卵睾型DSD和46,XX睾丸型DSD。该病可以导致高促性腺性性腺功能不良,故LH和FSH升高,尤其是FSH升高明显,故LH/FSH降低是其特点。NR5A1基因突变的治疗主要是对症治疗,性别认定需要结合多方面的因素,患儿在青春期前可以使用GnRHa抑制性腺发育以避免性腺功能早衰。该文就NR5A1的研究进展进行综述。展开更多
类固醇生成因子(SF-1,NR5A1)是在性腺及肾上腺发育过程中起关键调控作用的转录因子。NR5A1基因突变是性发育异常(disorders of sex development,DSD)常见病因之一,目前临床报道的病例多为杂合突变。该基因突变患者临床表型复杂,早期报...类固醇生成因子(SF-1,NR5A1)是在性腺及肾上腺发育过程中起关键调控作用的转录因子。NR5A1基因突变是性发育异常(disorders of sex development,DSD)常见病因之一,目前临床报道的病例多为杂合突变。该基因突变患者临床表型复杂,早期报道的患者表现为不同程度的46,XY性腺发育不良,近年发现该基因突变与男性无精症或女性的卵巢早衰有关,多数患者无肾上腺皮质功能不全。目前认为患者临床表型异质性,可能与不同基因突变对转录活性的功能影响、下游靶基因(如SOX9等)基因剂量效应以及寡基因突变等的遗传背景等相关。通过对NR5A1突变的基因型和相关表型开展研究,有助于人们深入理解性腺发育的过程及其调控机制。展开更多
文摘目的分析XY女性性逆转患者核受体亚家族5,组A,成员1(nuclear receptor subfamily 5 group A member 1,NR5A1)基因的基因突变情况。方法抽提样本外周血白细胞的DNA,对NR5A1的2~7外显子进行PCR扩增,扩增产物直接测序,重复实验和克隆测序实验验证检测到的突变,酶切分析筛查110名正常人群排除突变的多态性。结果在5例样本中未检出明显异常的突变,只在样本4中检出1个多态突变(p.G146A),该突变在正常对照人群中检出了37.3%的突变率。结论尽管在本研究中只检出1个基因多态突变,但结合国外报道,NR5A1的基因突变和性逆转的发生还是存在相关性。
基金supported by grants from the National Key Research and Development Program of China (No.2018YFC1003602 to HC and No.2018YFC1003504 to HJ)the National Natural Science Foundation of China (No.81871202 to HC and No.31900484 to GCX)+2 种基金Lo Kwee Seong Start Up Fund to KLE,Shanghai Sailing Program (No.20YF1422900 to YWZ)the Natural Science Foundation of Nantong (No.JC2021081 to JWS)Startup R&D funding from Nantong University (No.135419631032 to JWS and TDYX2021021 to JWS).
文摘This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development(DSD)patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1(NR5A1)gene.Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1.The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development.The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis.Microfluidic-based single-cell RNA sequencing(scRNA-seq)analysis found that the fibroblast cells were significantly increased(approximately 46.5%),whereas the number of main epididymal epithelial cells(approximately 9.2%),such as principal cells and basal cells,was dramatically decreased.Bioinformatics analysis of cell–cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition(EMT)process.The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.
文摘目的探讨1例46,XY性发育异常(disorders of sex development,DSD)患儿的遗传学机制,并分析其基因型与表型的相关性。方法对患儿进行全外显子组测序,并对其NR5A1基因的第1~7外显子进行多重连接探针扩增检测。结果患儿表现为幼稚女童外阴,Tanner分期为1期。B超可见卵巢和子宫。患儿外周血染色体核型为46,XY,全外显子组测序发现其携带NR5A1基因第5外显子杂合缺失(chr9q33.3:127255298-127255438),为新发现的致病变异,遗传自母亲,父亲未见异常。结论46,XY DSD患儿主要表现为外生殖器男性化不足,NR5A1基因变异是其重要的遗传学病因。全外显子组测序提高了基因变异的检出率,为患儿家庭的遗传咨询提供了确切的依据。
文摘目的探究46,XY女性性逆转患者与核受体亚家族5组A成员1(nuclear receptor subfamily 5 group A member 1,NR5A1)基因突变的相关性。方法通过染色体核型分析选取符合条件的样本,提取外周血全基因组DNA,对NR5A1基因的6个(2~7)外显子进行PCR扩增,所得产物经过电泳后直接测序,并进行重复实验验证检测到的突变,同时以102名正常人群作为对照组,排除基因多态性的影响。结果在7例样本中未检出新的突变,在样本1,4,5中检出1个多态突变(p.G146A),该突变在正常对照人群中检出了43.14%的突变率;在样本1和3的5号外显子中发现Q314Q(C.942G>A,rs201103618),在样本2的4号外显子发现了P130P(C.390G>C),在其他外显子中没有发现突变。结论分析本研究的实验结果并结合国内外的相关资料报道,在四川地区,NR5A1基因突变和46,XY女性性逆转的发生可能存在相关性,进一步的深入研究是有必要的。
文摘NR5A1基因突变是46,XY性发育异常(46,XY disorder of sex development,46,XYDSD)常见的病因之一,为常染色体显性遗传病,其临床表型多样。46,XY性腺发育不良是最常见的临床表现,特定位点突变的患儿可出现肾上腺功能不良,一些患儿的身高可受影响。近年来越来越多的研究证明,NR5A1基因突变可以导致46,XX卵睾型DSD和46,XX睾丸型DSD。该病可以导致高促性腺性性腺功能不良,故LH和FSH升高,尤其是FSH升高明显,故LH/FSH降低是其特点。NR5A1基因突变的治疗主要是对症治疗,性别认定需要结合多方面的因素,患儿在青春期前可以使用GnRHa抑制性腺发育以避免性腺功能早衰。该文就NR5A1的研究进展进行综述。
文摘类固醇生成因子(SF-1,NR5A1)是在性腺及肾上腺发育过程中起关键调控作用的转录因子。NR5A1基因突变是性发育异常(disorders of sex development,DSD)常见病因之一,目前临床报道的病例多为杂合突变。该基因突变患者临床表型复杂,早期报道的患者表现为不同程度的46,XY性腺发育不良,近年发现该基因突变与男性无精症或女性的卵巢早衰有关,多数患者无肾上腺皮质功能不全。目前认为患者临床表型异质性,可能与不同基因突变对转录活性的功能影响、下游靶基因(如SOX9等)基因剂量效应以及寡基因突变等的遗传背景等相关。通过对NR5A1突变的基因型和相关表型开展研究,有助于人们深入理解性腺发育的过程及其调控机制。