SRY (sex-determining region Y chromosome) is considered as a strong candidste for the TDF (testis determining factor) and has been cloned following another candidate ZFY (zinc finger protein gene). In this study,eight...SRY (sex-determining region Y chromosome) is considered as a strong candidste for the TDF (testis determining factor) and has been cloned following another candidate ZFY (zinc finger protein gene). In this study,eight cases of sex revelsal, including four 46, XX males and four 46, XY females aere examined for the presence of SRY sequence and a Y-repeated DNA locus. Our data indicated that the genownic DNA of the four classical 46,XX males had the SRY sequences. On the other hand, both SRY sequences and Ye repeated DNA sequences were present in all four 46, XY females.These resultssuavest that SAY sequences were responsible for the sexraversal of 46, XX males Whereas there may be other genetic mechanisms forthe sex reversal of 46, XY females Without the lack of SRY sequences.展开更多
目的探讨46,XY性反转的发病机制。方法分析6例46,XY性反转患者的临床表现和体征并结合文献复习。结果 6例患者的临床表现和体征差异较大,细胞遗传学检查和性腺组织病理学检查结果也不一致。结论在46,XY性反转的发病原因中,虽然SRY基因(S...目的探讨46,XY性反转的发病机制。方法分析6例46,XY性反转患者的临床表现和体征并结合文献复习。结果 6例患者的临床表现和体征差异较大,细胞遗传学检查和性腺组织病理学检查结果也不一致。结论在46,XY性反转的发病原因中,虽然SRY基因(Sex-determining region Y)的异常是主因之一,但同时还有其它众多性别决定基因参与作用。提示我们,今后对该病应加强对性腺分化发育的分子机制、信号通路及调控进行分子遗传学研究,寻找产前诊断的分子遗传学标志,预防此类患儿的出生。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
BACKGROUND Androgen insensitivity syndrome is an X-linked recessive genetic disease caused by mutations in the androgen receptor gene(AR).However,the underlying molecular mechanisms for the majority of AR variants rem...BACKGROUND Androgen insensitivity syndrome is an X-linked recessive genetic disease caused by mutations in the androgen receptor gene(AR).However,the underlying molecular mechanisms for the majority of AR variants remain unclear.In this study,we identified a point variant in three patients with complete androgen insensitivity syndrome(CAIS),summarized the correlation analysis,and performed a literature review.CASE SUMMARY The proband was raised as a girl.In infancy,she was first referred to hospital with a right inguinal hernia.Ultrasonography revealed the absence of a uterus and ovaries,and a testis-like structure located at the inguinal canal.Further diagnostic workup detected a 46,XY karyotype,and fluorescence in situ hybridization analysis showed the presence of the SRY gene.Histological analysis revealed the excised tissue to be testicular.Twelve years later,she was admitted to our hospital with a lack of breast development.Her pubic hair and breasts were Tanner stage I.She had normal female external genitalia.Blood hormone tests showed normal testosterone levels,low estradiol levels,and high gonadotropin levels.Her two siblings underwent similar examinations,and all three had a rare hemizygous missense mutation in AR:c.2678C>T.In vitro functional analyses revealed decreased nuclear translocation in AR-c.2678C>T mutation cells.CONCLUSION This case of CAIS was caused by an AR variant(c.2678C>T).Functional studies showed impaired nuclear translocation ability of the mutant protein.展开更多
文摘SRY (sex-determining region Y chromosome) is considered as a strong candidste for the TDF (testis determining factor) and has been cloned following another candidate ZFY (zinc finger protein gene). In this study,eight cases of sex revelsal, including four 46, XX males and four 46, XY females aere examined for the presence of SRY sequence and a Y-repeated DNA locus. Our data indicated that the genownic DNA of the four classical 46,XX males had the SRY sequences. On the other hand, both SRY sequences and Ye repeated DNA sequences were present in all four 46, XY females.These resultssuavest that SAY sequences were responsible for the sexraversal of 46, XX males Whereas there may be other genetic mechanisms forthe sex reversal of 46, XY females Without the lack of SRY sequences.
文摘目的探讨46,XY性反转的发病机制。方法分析6例46,XY性反转患者的临床表现和体征并结合文献复习。结果 6例患者的临床表现和体征差异较大,细胞遗传学检查和性腺组织病理学检查结果也不一致。结论在46,XY性反转的发病原因中,虽然SRY基因(Sex-determining region Y)的异常是主因之一,但同时还有其它众多性别决定基因参与作用。提示我们,今后对该病应加强对性腺分化发育的分子机制、信号通路及调控进行分子遗传学研究,寻找产前诊断的分子遗传学标志,预防此类患儿的出生。
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。
基金the key Research and Development Program of Zhejiang Province,No.2020C03121.
文摘BACKGROUND Androgen insensitivity syndrome is an X-linked recessive genetic disease caused by mutations in the androgen receptor gene(AR).However,the underlying molecular mechanisms for the majority of AR variants remain unclear.In this study,we identified a point variant in three patients with complete androgen insensitivity syndrome(CAIS),summarized the correlation analysis,and performed a literature review.CASE SUMMARY The proband was raised as a girl.In infancy,she was first referred to hospital with a right inguinal hernia.Ultrasonography revealed the absence of a uterus and ovaries,and a testis-like structure located at the inguinal canal.Further diagnostic workup detected a 46,XY karyotype,and fluorescence in situ hybridization analysis showed the presence of the SRY gene.Histological analysis revealed the excised tissue to be testicular.Twelve years later,she was admitted to our hospital with a lack of breast development.Her pubic hair and breasts were Tanner stage I.She had normal female external genitalia.Blood hormone tests showed normal testosterone levels,low estradiol levels,and high gonadotropin levels.Her two siblings underwent similar examinations,and all three had a rare hemizygous missense mutation in AR:c.2678C>T.In vitro functional analyses revealed decreased nuclear translocation in AR-c.2678C>T mutation cells.CONCLUSION This case of CAIS was caused by an AR variant(c.2678C>T).Functional studies showed impaired nuclear translocation ability of the mutant protein.
