10例性分化异常患者的SRY基因检测

目的：研究性分化异常患者的染色体核型和SRY基因在性分化异常中的作用。方法：采用常规G显带方法分析10例性分化异常患者的染色体核型并通过应用PCR技术扩增SRY基因。结果：10例性分化异常患者中,有5例男性患者染色体核型为46,XX,其SRY基因为阴性,2例男性患者染色体核型为46,XX,其SRY基因为阳性,2例女性患者染色体核型为46,XY,其SRY基因为阳性,1例女性患者染色体核型为46,XY／45,X,其SRY基因为阳性。结论：性分化异常患者的染色体核型与其性腺性别不相符,SRY基因是在性分化异常中睾丸分化和发育的关键基因。     

SRY基因突变和性腺肿瘤发生的研究Ⅰ．家族性46，XY女性SRY基因检测

近年证明ＳＲＹ男性性基因是性别决定关键。ＳＲＹ突变能引起男性性异常。４６，ＸＹ性腺发育不全（或ＸＹ女性）系ＳＲＹ基因突变所致，并有高发性腺肿瘤特点。ＳＲＹ突变有多种类型；本研究检测一家庭集聚性ＸＹ女性高发肿瘤成员有个ＳＲＹ基因缺失。结合细胞遗传学和病理学检查结果，对ＸＹ女性性腺癌变机理提出了推测。     

A novel mutation in the SRY gene of a Chinese 46,XY female patient with unilateral mixed germ cell tumor

Objective To determine the nosogenetic factors of a 46,XY female with primary amenorrhea and unilateral mixed germ cell tumor.Methods Eight genes associated with 46,XY gonadal dysgenesis were detected in the patient and her parents by target region captured-next generation sequencing.Results An insertion of a single nucleotide(adenine) at the coding site 230(c.230_231insA) located in the high mobility group(HMG) domain of SRY was revealed,which led to a truncated protein(p.Lys77 fsX 27). This mutation was at position 2655414 of the Y chromosome, supported with 127 unique mapped reads, however, this mutation was not found in the in-house dataset of 1 092 controls. Additionally, none of the candidate gene was detected in the patient's parents, which indicated that it is a de novo mutation.Conclusion A novel SRY sporadic mutation due to a single nucleotide insertion at position 230(c.230_231insA) was identified as the cause of the disease in this patient.Target region captured-next generation sequencing was found to be an effective method for the molecular genetic testing of 46,XY complete gonadal dysgenesis(46,XY CGD).     

原发性闭经患者染色体核型分析及SRY基因检测

目的:分析原发性闭经患者染色体异常核型及Y染色体上的性别决定区(SRY)基因,并对原发性闭经的原因进行探讨.方法:采用染色体G显带及聚合酶链反应对71例原发性闭经患者进行染色体核型分析及SRY基因检测.结果:71例原发性闭经患者中检出核型异常者23例;6例SRY阳性.其中45X 7例、45X/46XX1例、45X/46Xi(Xq)3例、46Xi(Xq)6例、46XX/46XY 2例、46XY 4例.1例45X/46Xi(Xq)SRY基因为阳性,2例46XX/46XY均检测出SRY基因,4例46XY中3例SRY阳性,其余患者SRY基因均为阴性.结论:染色体核型异常与SRY基因异常均可导致原发性闭经.     

利用PCR，FISH对异常核型中额外染色体的证实

目的：检测在常规G显带下，45，X［115］/46，X+mar［45］/46，XY［29］异常核型中额外小染色体的来源。方法：利用PCR对SRY基因进行检测；对人的Y染色体进行标记，利用荧光原位杂交技术，在荧光显微镜下观察。结果：用Y染色体杂交，发现在额外小染色体上有荧光信号。结论：额外小染色体来源于Y染色体。     

单纯性XY性腺发育不全

本文报道5例单纯性性晚发育不全(Swyer综合征)。基因型为46,XY,表现型为女性伴性腺发育不全。3例为家族性,2例为散发性。临床特征为女性表现型,原发闭经,无青春期变化。所有患者均有幼稚子宫、正常输卵管、条索状性腺和女性外生殖器。2例有性母细胞瘤。讨论了发病机理、性腺肿瘤和处理等问题。     

46,XY单纯性性腺发育不全的临床分析

 目的 探讨染色体核型为46,XY单纯性性腺发育不全患者(合并或不合并卵巢肿瘤)的诊断和治疗。方法 分析1991年7月至2011年8月我院收治的6例染色体核型为46,XY单纯性性腺发育不全病例。所有病例均行剖腹探查术或腹腔镜手术。结果 所有患者的临床表现为原发闭经或继发闭经;乳房不发育或发育欠佳;阴毛、腋毛无或稀少;内外生殖器幼稚,有输卵管、卵巢、子宫及阴道。实验室检查FSH,LH均明显高于正常水平;染色体检查为46,XY。手术切除双侧性腺,病理提示6名患者中有4例发生卵巢肿瘤,肿瘤发生率高达66.7%。结论 及时确诊46,XY单纯性性腺发育不全十分重要,确诊后需立即切除双侧性腺以避免肿瘤的发生。     

性发育异常的细胞和分子遗传学分析

目的：探讨染色体核型分析及SRY基因检测在性发育异常中的意义。方法：通过染色体G显带及聚合酶链式反应(PCR)对13例性发育异常患者进行染色体核型及睾丸决定基因(SRY)分析。结果：3例46，XX男性，SRY基因阳性：3例46，XY女性，SRY基因阳性；2例46，XY男性，SRY阴性：1例46，XY女性，SRY阴性1例45，X／46，XX／46，X，-X， mar男性，SRY阴性；1例47，XXY男性，SRY阳性1例46，X，-X， mar女性，SRY阳性；1例45，X／46，XY女性，SRY阳性。结论：性染色体异常和SRY基因异常均能导致性分化及发育异常。     

138例闭经的细胞遗传学分析

本文对138例闭经患者进行了遗传咨询及外周血G显带染色体研究。其中发现核型异常的为51例,占37%。51例中有先天性卵巢发育不全49例,混合性腺发育不全2例。另外,138例中尚有11例为46,XY核型,占7.97%。     

性反转综合征的细胞遗传学1例分析

目的: 探讨性反转综合征发病的可能原因。方法: 运用人类外周血淋巴细胞常规染色体核型并结合相关文献资料进行分析。结果: 分析30个中期分裂相,核型均为46,XY。结论: 该女性患者为46,XY男性性反转综合征;SRY基因的突变或缺失以及SOX基因的突变是导致性反转综合征的主要原因。     

Investigation of SRY Gene in Sex Reversed Syndrome Patients

SRY (sex-determining region Y chromosome) is considered as a strong candidate for the TDF (testis determining factor) and has been cloned following another candidate ZFY (zinc finger protein gone). In this study,eight cases of sex reversal, including four 46, XX males and four 46, XY females were examined for the presence of SRY sequence and a Y-repeated DNA locus. Our data indicated that the genomie DNA of the four classical 46,XX males had the SRY sequences. On the other hand, both SRY sequences and Y-repeated DNA sequences were present in aii four 46, XY females.These results suggest that SRY sequences were responsible for the sex reversal of 46, XX males whereas there may be other genetic mechanisms for the sex reversal of 46, XY females without the lack of SRY sequences.     

PATHOLOGICAL CHARACTERISTICS OF GONADS IN NINE PATIENTS WITH TRUE HERMAPHRODITISM

The gonadal histopathology, and its correlation with the clinical features has been investigated in 9 true hermaphroditism patients, aged 5-21 yr. Seven of 9 patients had been raised as females, of which the chromosomal karyotype was 46XX in 5 cases, 46XX/46XY and 46XX/47XXY in 2 cases. Two of 9 patients were raised as males, the chromosomal karyotypes being 46XX and 46XX/46XY. All 9 patients had testieular tissue excised, and biopsies of the conserved ovaxian tissue were performed. Ovotestis was the most common form of the abnormal gonads; two of 9 patients had bilateral ovotestes, seven had unilsteral ovotestes (5 in right side, 2 in left side). In seven patients with a unilateral ovotestis, 6 had a contralateral ovary and one had a contralateral testis. Microscopically, the ovarian tissue of 11 ovotestes, including 6 biopsies from contealateral ovaris, were normal, with many primordal follicles and a few growing follicles.In two of the patients, aged over 15 years, evidence of ovulation was observed. In comparison, the testicular tissue of the ovotestis and the one left inguinal testis was histologically abnormal, with immature seminiferous tubbers, most of which filled with Sertoli cells only, Three of 9 patients married after surgical treatment. Two of these subsequently conceived and delivered of normal infants by cesarean section.     

Twin dilivery of a 46,XY gonadal dysgenetic woman following vitrified oocytes donation

A 46,XY gonadal dysgenetic woman gave birth to two healthy girls following vitrified oocytes donation. The loss of SRY gene was considered as the cause of this patient. Although similar cases have been reported about pregnancies of 46,XY pure gonadal dysgenetic women, successful delivery from vitrified oocytes has been hardly reported yet. Oocytes vitrification technique provides a beneficial way by saving superfluous oocytes from the pregnancy patients to these women who need.

     

Twin delivery of a 46,XY gonadal dysgenetic woman following vitrified oocytes donation

A 46,XY gonadal dysgenetic woman gave birth to two healthy girls following vitrified oocytes donation. The loss of SRY gene was considered as the cause of this patient. Although similar cases have been reported about pregnancies of 46,XY pure gonadal dysgenetic women, successful delivery from vitrified oocytes has been hardly reported yet. Oocytes vitrification technique provides a beneficial way by saving superfluous oocytes from the pregnancy patients to these women who need.     

性反转综合征患者SRY基因检测及病因分析

目的 研究性反转综合征的发生与性别决定基因SRY（sex-determining region on the Ychromosome）之间的关系。方法 应用聚合酶链反应（polymerase-chain reaction，PCR）对2例46，XX男性性反转及1例46，XY女性性反转患者进行SRY扩增，并将扩增产物在ABI-377测序仪上测序。结果 2例46，XX男性性反转患者SRY检测1例阳性，1例阴性。46，XY女性性反转患者SRY阳性，2个SRY阳性病例DNA序列分析均未检测到突变。结论 SRY是性别决定和分化的重要基因，SRY阴性XX男性性反转及SRY阳性但无突变的XY女性性反转的发生，可能与其它性别分化相关基因的异常有关。     

46,XY性反转综合征的分子病因研究

采用ＰＣＲ技术，对３例４６，ＸＹ女性性反转综合征患者外周血基因组ＤＮＡ进行了ＳＲＹ基因扩增。结果表明，例１ＳＲＹ基因缺失，例２、例３存在ＳＲＹ基因，进一步证明ＳＲＹ基因作为性别决定基因的重要作用，同时也表明，性反转综合征病因的多样性和性别决定机制的复杂性。     

46,XY单纯性腺发育不全的治疗(附2例报告)

目的 探讨46,XY单纯性腺发育不全病人的病因、临床表现及治疗方法 .方法 对2例染色体核型为46,XY单纯性腺发育不全病人的临床资料进行分析.结果 2例病人的生长和智力发育均正常,两臂与地平行伸展开两手中指的距离等于身高.原发闭经,青春期有女性第二性征发育,有阴毛、腋毛,乳房发育可.病人均有阴道, 行人工周期月经治疗有效.2例行腹腔探查术,术中均可见到发育不良的子宫、发育欠佳的输卵管、条索状性腺组织以及实性包块.手术切除包块及条索状性腺组织,病理诊断均为无性细胞瘤.结论 对生殖器官发育不良病人应常规行染色体检查;对46,XY单纯性腺发育不全病人应尽早切除性腺,通过性激素替代治疗提高病人生活质量.     

Familial dysgerminoma associated with 46, XX pure gonadal dysgenesis

Although the occurrence of pure gonadal dysgenesis PGD is usually sporadic and nonfamilial, here we present 3 sisters with 46, XX PGD, who are born from a first cousin marriage. Review of their family pedigree is compatible with autosomal recessive inheritance. Surprisingly, 2 of these sisters developed ovarian tumors. Both showed the pathological result of dysgerminoma with syncytiotrophoblastic giant cells. These 2 cases are examples of tumorigenesis in PGD without an identifiable Y chromosome. Therefore, malignant degeneration of the streak gonads should be considered in the patients with 46, XX PGD.     

用母体外周血中胎儿游离DNA检测胎儿SRY基因的研究

目的探索从孕妇外周血浆中检测胎儿躲y基因的高灵敏性及高准确性方法。方法应用PcR、实时荧光定量PcR、PEP—PcR技术,检测33例妊娠8～14周的正常孕妇血浆中游离胎儿DNA的脓y基因。组织标本躲y基因检测结果作为性别判定的标准。结果33例孕妇血浆标本检测职y基因,普通PcR检出的灵敏性为58．82％,特异性100％。PEP—PCR的灵敏性为88．24％,特异性100％。荧光定量PCR的灵敏性为88．24％,特异性100％。结论PEP—PCR技术和荧光定量PcR技术均可以提高胎儿游离DNA检测的灵敏度及准确性．可用于进一步染色体疾病的无创性产前筛查研究。     

性发育异常患者SRY基因分析

应用ＳＲＹ基因编码区１对特异寡核苷酸引物进行基因组ＤＮＡ扩增,结合单链构象多态性分析,银染显色,探讨性别决定基因（ｓｅｘ－ｄｅｔｅｒｍｉｎｉｎｇ ｒｅｇｉｏｎ ｏｎ Ｙ, ＳＲＹ）对性发育异常患者临床诊断的意义。结果：５例患者中,２例４６,ＸＸ男性显示与男性相同的特异扩增带;３例４６,ＸＹ女性中２例无男性特异扩增带,１例显示ＳＲＹ基因片段扩增,经单链构象多态性分析,显示与正常男性扩增片段相同的单链泳动带型。支持ＳＲＹ基因是男性性别决定的关键基因的假说,提示ＳＲＹ基因的调节基因等可能参与协同作用。