The Swyer’s syndrome, 46XY gonadal dysgenesis ( 46XYGD) or XY female, belongs to the category of sexual abnomality. The syndrome is characterized by a female phenotype with streak gonads, 46XY karyotype and complic...The Swyer’s syndrome, 46XY gonadal dysgenesis ( 46XYGD) or XY female, belongs to the category of sexual abnomality. The syndrome is characterized by a female phenotype with streak gonads, 46XY karyotype and complicated by frequent develop of gonadal tumors. A congragated familial 46XYGD was analyzed. We have examined the whole family from many aspects and have followed the affected members more than 10 years. In present case , all eight siblings phenotypically were girls ; the two eldest members died between 1970 1972 from embryonic gonadal tumors. Five of remaining 6 girls were affected by the syndrome of 46 XYGD and two have got the same kind of tumor dysgerminoma. By cytogenetic and cytobiological studies and on the basis of accumulated data the mechanism of gonadal carcinogenesis was analyzed. The origin of dysgerminoma for 46XYGD syndrome was postulated.展开更多
目的探讨46,XY性发育异常(disorders of sex development,DSD)的不同表型与单基因变异的关联性。方法收集2018年2月至2018年11月间浙江大学医学院附属儿童医院137例临床诊断为46,XYDSD的病例,并提取外周血基因组DNA。采用液相捕获技术...目的探讨46,XY性发育异常(disorders of sex development,DSD)的不同表型与单基因变异的关联性。方法收集2018年2月至2018年11月间浙江大学医学院附属儿童医院137例临床诊断为46,XYDSD的病例,并提取外周血基因组DNA。采用液相捕获技术靶向捕获2742个疾病基因,通过高通量测序和生物信息学方法获取基因编码区和临近10bp区域的变异,参考ACMG分类标准进行分级。将测试病例按临床表型分为“隐睾或小睾丸、尿道下裂、小阴茎或隐匿性阴茎、多种DSD表型、性别模糊、综合征型DSD”六组。计算不同表型与基因变异对46,XYDSD的阳性检出率、辅助诊断率。结果137例中有62例检出具备临床参考价值的变异,涉及SRD5A2、AR、NR5A1、AMH、FGFR1、PROKR2、DMRT1、MAmLD1、WT1、ZEB2、AKR1C2、CHD7、CYP17A1、DMRT2、FGD1、FRAS1、GATA4、MAP3K1、POR、SAMD9、TACR3、VANGL1、WNT5A共23个基因,综合阳性检出率为45.26%。62例中36例检出能解释临床表型的基因变异,涉及SRD5A2、AR、NR5A1、AMH、FGFR1、PROKR2、DMRT1、MAmLD1、WT1、ZEB2共10个基因,辅助诊断率为26.28%。隐睾或小睾丸、尿道下裂、小阴茎或隐匿性阴茎、多种DSD表型、性别模糊、综合征型DSD的阳性检出率分别为8.33%、26.32%、38.71%、57.14%、86.36%、66.67%,其辅助诊断率分别为0.00%、15.79%、16.13%、28.57%、63.64%、50.00%。结论单基因变异是46,XYDSD的重要遗传学病因之一,基因变异的阳性检出率和辅助诊断率均与临床表型的多样性及严重程度呈正相关;靶向捕获疾病基因联合高通量测序可作为“性别模糊、综合征型DSD、多种DSD表型”46,XYDSD遗传学测试的首选方法。展开更多
文摘The Swyer’s syndrome, 46XY gonadal dysgenesis ( 46XYGD) or XY female, belongs to the category of sexual abnomality. The syndrome is characterized by a female phenotype with streak gonads, 46XY karyotype and complicated by frequent develop of gonadal tumors. A congragated familial 46XYGD was analyzed. We have examined the whole family from many aspects and have followed the affected members more than 10 years. In present case , all eight siblings phenotypically were girls ; the two eldest members died between 1970 1972 from embryonic gonadal tumors. Five of remaining 6 girls were affected by the syndrome of 46 XYGD and two have got the same kind of tumor dysgerminoma. By cytogenetic and cytobiological studies and on the basis of accumulated data the mechanism of gonadal carcinogenesis was analyzed. The origin of dysgerminoma for 46XYGD syndrome was postulated.
文摘目的探讨46,XY性发育异常(disorders of sex development,DSD)的不同表型与单基因变异的关联性。方法收集2018年2月至2018年11月间浙江大学医学院附属儿童医院137例临床诊断为46,XYDSD的病例,并提取外周血基因组DNA。采用液相捕获技术靶向捕获2742个疾病基因,通过高通量测序和生物信息学方法获取基因编码区和临近10bp区域的变异,参考ACMG分类标准进行分级。将测试病例按临床表型分为“隐睾或小睾丸、尿道下裂、小阴茎或隐匿性阴茎、多种DSD表型、性别模糊、综合征型DSD”六组。计算不同表型与基因变异对46,XYDSD的阳性检出率、辅助诊断率。结果137例中有62例检出具备临床参考价值的变异,涉及SRD5A2、AR、NR5A1、AMH、FGFR1、PROKR2、DMRT1、MAmLD1、WT1、ZEB2、AKR1C2、CHD7、CYP17A1、DMRT2、FGD1、FRAS1、GATA4、MAP3K1、POR、SAMD9、TACR3、VANGL1、WNT5A共23个基因,综合阳性检出率为45.26%。62例中36例检出能解释临床表型的基因变异,涉及SRD5A2、AR、NR5A1、AMH、FGFR1、PROKR2、DMRT1、MAmLD1、WT1、ZEB2共10个基因,辅助诊断率为26.28%。隐睾或小睾丸、尿道下裂、小阴茎或隐匿性阴茎、多种DSD表型、性别模糊、综合征型DSD的阳性检出率分别为8.33%、26.32%、38.71%、57.14%、86.36%、66.67%,其辅助诊断率分别为0.00%、15.79%、16.13%、28.57%、63.64%、50.00%。结论单基因变异是46,XYDSD的重要遗传学病因之一,基因变异的阳性检出率和辅助诊断率均与临床表型的多样性及严重程度呈正相关;靶向捕获疾病基因联合高通量测序可作为“性别模糊、综合征型DSD、多种DSD表型”46,XYDSD遗传学测试的首选方法。
