5例SRY阴性的46,XX男性综合征遗传学分析

目的通过对5例SRY阴性的46,XX男性综合征患者进行细胞及分子遗传学分析,探讨性分化异常的机制。方法外周血淋巴细胞染色体核型分析;提取外周血基因组DNA,进行SRY基因、Y染色体AZF区域微缺失检测。结果 5例患者染色体核型分析均为46,XX,PCR扩增显示SRY基因、AZFa、b、c区全部缺失。结论 SRY基因缺失的患者也能发育成临床男性表型,提示在男性性别的决定和分化过程中,SRY基因并不是唯一基因。     

2例SRY阳性的46,XX男性综合征患者临床及细胞分子遗传学研究

目的探讨SRY阳性的46,XX男性综合征患者的临床及细胞分子遗传学特征。方法分析2例46,XX(SRY+)男性综合征患者的临床特点,通过患者染色体核型分析、多重连接探针扩增(MLPA)、荧光原位杂交(FISH)技术,进行Y染色体微缺失的细胞和分子遗传学检测。结果 2例患者社会性别均为男性,染色体核型均为46,XX,Y染色体微缺失检测示AZF a,b,c区域均缺失,SRY基因均存在。结论 SRY基因是参与性别决定和分化的关键基因,对其进行检测有利于明确性反转综合征的临床诊断,细胞、分子遗传学研究为性发育异常患者的临床确诊和治疗提供了依据。     

一例SRY阳性的46,XX男性综合征患者临床及细胞遗传学研究

目的探讨SRY阳性的46,XX男性综合征患者的临床及细胞遗传学研究。方法针对1例SRY阳性的46,XX男性综合征患者,应用多重PCR及染色体技术进行SRY、Y染色体微缺失等细胞遗传学检测。结果通过PCR扩增SRY、Y染色体微缺失发现患者SRY基因阳性,且Y染色体微缺失AZF区域AZFa、AZFb、AZFc、AZFd均缺失。染色体核型为46,XX。性激素检测示高促性腺激素性腺功能不全。结论对性发育异常的患者进行染色体核型分析和SRY基因检测,有利于了解该类患者的遗传学病因,为明确诊断和治疗提供科学依据。     

46,XX男性/46,XY女性综合征病例分析

目的报告2例性反转综合征病例,探讨性反转综合征的遗传学机制及性别决定基因在人类性腺分化和性别发育中的作用。方法细胞遗传学染色体核型分析以及PCR技术检测外周血SRY基因。结果病例1患者的外周血染色体核型为46,XX,SRY( )。诊断为46,XX男性性反转综合征;病例2的患者外周血染色体核型为46,XY,SRY( )。诊断为46,XY女性性反转综合征。结论细胞遗传学核型分析结合PCR技术检测SRY基因,是诊断性别发育异常患者的重要手段。SRY基因检测比Y染色体更能预示睾丸组织的存在。除SRY基因外,还存在多个参与性别决定和分化的基因,性分化异常表现高度遗传异常性。     

安徽地区87例男性不育患者的遗传学病因分析

目的研究染色体异常、SRY基因突变及Y染色体AZF基因微缺失等遗传学病因与男性不育的关系。方法采用染色体G显带对87例男性不育患者进行核型分析,采用PCR技术对患者SRY基因突变及Y染色体AZF基因微缺失进行检测。结果87例男性不育患者中发现染色体异常25例（28．74％）;XX男性反转1例（1．15％）;AZF微缺失4例（4．60％）。总的遗传学异常检出率为34．48％。结论染色体异常及Y染色体AZF微缺失等是引起男性不育的重要遗传学病因。     

应用FISH和PCR方法对性发育异常患者……

目的： 应用FISH和PCR方法对7例性发育异常患者进行明确的遗传学诊断，分析患者性发育异常产生的原因。方法： 采用CEPX-Yq21双色探针及SRY特异探针进行原位杂交，分析患者X、Y染色体及SRY基因的分布情况。PCR的方法检测Y染色体短臂SRY、ZFY基因和Y染色体长臂AZF因子，确定Y染色体的完整性。结果：病例①②表型男，染色体核型为嵌合型分别是46，XX/46，XY；46，XX/46，XY/47，XXY，①AZF多个位点缺失，②AZF无位点缺失。病例③表型男，核型46，XX，SRY基因阳性位于Xp。病例④表型男，核型45，X，SRY阳性。病例⑤表型男，核型46，XX，SRY阴性。病例⑥表型女，核型46，XY， SRY阴性。病例⑦表型女，核型46，XX， SRY阴性ZFY阳性。结论：性染色体畸变是引起性发育异常的重要原因之一 ,Y染色体在性别分化中起睾丸决定作用，SRY基因是性别决定的主导基因，但不是决定全部男性化的惟一因素。     

二例男性性反转综合征临床特征及细胞分子遗传学检测分析

目的探讨男性性反转综合征患者的临床表现及细胞分子遗传学特征。方法分析2例男性反转综合征患者的临床表现,并进行性激素、染色体核型分析、Y染色体微缺失、SRY基因等检测。结果 2例患者社会性别均为男性,1例身材低于正常男性均值,1例身材高于正常男性均值。均因不育就诊,阴茎发育正常,双侧睾丸体积小、质地软,精液检查均为无精子症。性激素检查示高促性腺激素性性腺功能不全,染色体核型均为46,XX,Y染色体微缺失检测示AZFa,b,c区域均缺失,SRY基因均存在。结论男性表型的性反转综合征患者身材不一定矮小,其睾丸发育不良,均不育。患者的男性表型是由于基因组中存在SRY基因,无精子表型是由于缺失AZF。     

应用FISH和PCR方法对7例性发育异常患者进行分子细胞遗传学研究

目的应用FISH和PCR方法对7例性发育异常患者进行明确的遗传学诊断,分析患者性发育异常产生的原因。方法采用CEPX-Yq21双色探针及SRY特异探针进行原位杂交,分析患者X、Y染色体及SRY基因的分布情况;PCR的方法检测Y染色体短臂SRY、ZFY基因和Y染色体长臂AZF因子,确定Y染色体的完整性。结果7例患者中,有5例社会性别为男性：染色体核型为2例46,XX,2例嵌合型46,XX／46,XY;46,XX／46,XY／47,XXY、1例45,X;2例社会性别为女性：1例46,XY,SRY基因阴性;1例46,XX,SRY阴性、ZFY基因阳性。46,XX男性患者中1例SRY基因位于Xp,1例为SRY阴性;嵌合型男性患者中1例AZF多个位点缺失,另1例AZF无位点缺失;45,X男性患者为SRY阳性。结论性染色体畸变是引起性发育异常的重要原因之一,Y染色体在性别分化中起睾丸决定作用,SRY基因是性别决定的主导基因,但不是决定全部男性化的惟一因素。     

性分化异常患者SRY基因的临床检测

目的　对社会性别为男性的性分化异常患者进行细胞遗传学检查和SRY基因分析以探讨其性别异常的原因。方法　外周血淋巴细胞培养法检查染色体核型 ,聚合酶链反应法 (PCR)检测SRY基因。结果　 5例患者染色体核型均为46 ,XX ,3例患者SRY基因存在 ,2例患者SRY基因缺失。结论　染色体检查、SRY基因检测在性分化异常患者的诊断和治疗中有重要意义 ,还有助于阐明性分化异常的遗传本质和发病机制     

睾丸生精功能障碍患者Y染色体微缺失及染色体核型分析

目的对睾丸生精功能障碍患者进行外周血染色体及Y染色体微缺失检测,探讨生精功能障碍的遗传学机制,为遗传咨询和临床治疗提供参考。方法对400例生精功能障碍患者进行染色体核型分析和Y染色体AZF基因微缺失检测,并对其结果进行分析。结果 120例无精子症患者中,核型异常36例,异常发生率30%,同时发现AZF微缺失14例,异常发生率11.67%;280例少精子症患者,核型异常34例,异常发生率12.14%,同时发现AZF微缺失16例,异常发生率5.71%。结论染色体异常和AZF的缺失是引起男性无精子和少精子并造成男性不育的重要原因之一,对男性不育人群进行细胞遗传学核型分析和和AZF检测十分必要。     

Genetic analysis for 2 females carrying idic(Y)(p) and with sex development disorders北大核心CSCD

Objective: To investigate the phenotype-genotype association of isodicentromere Y chromosome by analysis of two female patients carrying the chromosome with sexual development disorders. Methods: The karyotypes of the two patients were determined by application of conventional G banding of peripheral blood samples and fluorescence in situ hybridization (FISH). PCR was applied to detect the presence of SRY gene. Results: Conventional karyotype analysis showed case 1 to be a mosaic: mos. 45,X[38]/46,X,+mar[151]/47,XY,+mar[5]/47,X,+marX2[2]/46,XY[4], FISH showed that 12 different cell lines were presented in the karyotype of case 1 and partial cell lines with SRY gene, the marker is an isodicentromere Y chromosome[idic(Y)(p)]. No mutation was found in the SRY gene. The karyotype of case 2 was mos. 45,X[25]/46,X,+mar[35]. FISH showed the marker to be an idic(Y)(p) without the SRY gene. Conclusion: The karyotype of patients carrying idic(Y)(p) seems unstable, and female patients have the characteristics of short stature and secondary sexual hypoplasia. Karyotype analysis combined with FISH analysis can accurately determine the breakpoint of idic(Y) and identify the types of complex mosaic, which may facilitate genetic counseling and prognosis. © 2016, West China University of Medical Sciences. All rights reserved.     

Isodicentric Y (p11.32) chromosome in an infant with mixed gonadal dysgenesis

Among the structural abnormalities affecting the human Y chromosome, dicentric chromosomes are the most common. A wide spectrum of phenotypes of patients with a dicentric Y chromosome exists, ranging from almost males through mixed gonadal dysgenesis to females with Turner syndrome. Here, we describe an infant with mixed gonadal dysgenesis and mosaic karyotype 45,X/46,X,idic(Y)(qter-->p11.32:p11.32-->qter)/47,X,+2idic(Y) (qter-->p11.32:p11.32-->qter)/47,XYY. This was demonstrated by fluorescence in situ hybridization (FISH) analysis with whole Y chromosome painting (WCP-Y) probe. Molecular studies were performed on genomic DNA extracted from peripheral blood lymphocytes. To examine the sex determined region (SRY), azoospermia factor (AZF) region and deletion in azoospermia gene (DAZ), polymerase chain reaction (PCR) analyses were done with sequence-tagged site (STS) primers of 20 loci along the Y chromosome (SRY, DYS271, DYS148, DYS273, KALY, DYS212, SMCY, DYS215, DYS218, DYS219, DYS221, DYS223, DYS224, DYF51S1, DYS236, DAZ, DYS240), and all tested loci were found positive. Because of the possibility of a mutation in the SRY gene, we analyzed the PCR fragment by DNA sequencing and did not observe any mutation or nucleotide alteration. We present detailed molecular-cytogenetic characterization of a patient with idic(Y)(p11.32), and results are discussed with the previously described patients. As far as we know, this is the fifth report of a 46,X, idic(Y)(p11.32) karyotype and the first presentation with mixed gonadal dysgenesis and isodicentric Y. Since the correlation between phenotype and karyotype is not yet well defined, the clinical reports will be helpful in defining the phenotypic range of this chromosomal abnormality.     

True hermaphroditism with ambiguous genitalia due to a complicated mosaic karyotype: clinical features,cytogenetic findings,and literature review

Abnormal recombination between the X and Y chromosomes during meiosis, occurring outside the pseudoautosomal region, can result in translocation of the SRY gene from the Y to the X chromosome, and consequently in abnormal sexual differentiation, such as the development of 46,XX males or true hermaphroditism. In this report we present clinical, cytogenetic, and molecular-cytogenetic data of a patient with ambiguous genitalia and true hermaphroditism, who had a unique mosaic karyotype, comprising three different cell lines: 46,XX(SRY+), 45,X(SRY+), and 45,X. The mosaic karyotype of our patient probably represents two different events: abnormal recombination between the X and Y chromosomes during paternal meiosis, and postzygotic loss of one of the X chromosomes. Replication studies demonstrated that in 80% of the XX cells, the SRY sequence was located on the active X chromosome. This finding suggests nonrandom X inactivation and, together with the presence of the SRY gene, explains the male phenotype of our patient. On the other hand, the presence of the 45,X cell line may have contributed to genital ambiguity. We conclude that fluorescence in situ hybridization (FISH) analysis with SRY probes is highly recommended and allows accurate diagnosis and optimal management in cases of 46,XX hermaphroditism and ambiguous genitalia.     

应用FISH和PCR技术鉴别Turner综合征患者标记染色体起源

目的　为指导遗传咨询,鉴别Turner 综合征患者微小标记染色体起源。方法　选择SRY 基因编码区1 对特异寡核苷酸引物、X 和Y 染色体特异探针,采用PCR 及荧光原位杂交方法,对8 例具有Turner 综合征体征的患者进行标记染色体分析。结果　5 例患者标记染色体起源于X染色体;3 例起源于Y 染色体,其中2 例SRY 基因序列扩增,可见男性特异扩增带,另1 例无男性特异扩增带。结论　FISH 与PCR 技术结合可准确鉴别标记染色体,对选择治疗方案及了解核型与表型关系有指导意义。     

两性畸形患者性别决定基因研究

目的对5例两性畸形患者进行性别决定基因检测以探讨性别异常的原因。方法用聚合酶链反应（poiymerace chain reaction,PCR）的方法检测SRY基因。结果2例46,XY女性假两性畸形,SRY（＋）;2例46,XX男性假两性畸形,SRY（-）;1例46,XY原发性闭经,外观女性,SRY（＋）。结论两性畸形患者进行SRY基因检测对诊断及探讨其发病机制具有十分重要意义。     

两例Y染色体部分缺失胎儿的产前诊断

目的对两例Y染色体部分缺失胎儿进行产前诊断。方法采用常规G显带及C显带技术分析胎儿及父亲的核型,采用荧光原位杂交(fluorescence in situ hybridization,FISH)、染色体拷贝数变异检测技术(copy number varaition sequencing,CNV-seq)性别决定基因(sex region of Y chromosome,SRY)检测技术及无精子因子(azoospermia factor,AZF)检测技术检测胎儿DNAO结果2例胎儿羊水染色体在320〜400条带水平均提示46,XN,del(Y)(qll.2),Y染色体着丝粒探针FISH检测结果均提示Y染色体数目未见异常。2例胎儿父亲外周血染色体核型均未见明显异常。胎儿羊水DNA拷贝数检测提示一例胎儿Y染色体q 11.221-ql2处缺失12.88 Mb,涉及全部AZFb+AZFc区域;另一例胎儿Y染色体qll.21-ql2处缺失14.84 Mb,涉及全部AZF区域。2例胎儿羊水SRY基因检测提示SRY基因阳性,SKY基因编码区未检测到已报道的致病点突变。2例胎儿基因检测提示存在AZF部分或全部缺失。结论联合多种技术有助于明确诊断Y染色体结构异常。CNV-seq检测有利于快速筛查胎儿Y染色体微缺失,可做为对染色体核型分析的补充和验证的方法。     

46,XX男性与SRY基因关系的临床分析

目的 研究46,XX男性患者的临床表型与性别决定基因(sex determining region,SRY)的关系.方法 应用多重聚合酶链反应(polymerase chain reaction,PCR)及PCR产物直接测序的方法 ,对6例46,XX男性患者的SRY基因进行分析.结果 6例46,XX男性患者中3例SRY基因阳性,测序后无碱基序列变异,无明显的生殖器官畸形;3例患者SRY基因阴性,存在睾丸发育,但有明显的外生殖器官畸形.结论 在性别决定与发育过程中,SRY基因是一个关键的基因,但是还应有其他的重要基因.     

Sex chromosome mosaicism in gonads of a fetus with cystic hygroma and deletion of the short arm of Y chromosome including loss of SRY

The SRY gene on the short arm of the Y chromosome is necessary for male development. Without SRY, patients with 46,XY karyotype develop as females, fail to achieve normal puberty and have dysgenic gonads and a high incidence of gonadoblastoma. Here we report a female fetus, aborted at 17 weeks of pregnancy, with a non-mosaic 46,X,del(Y)(p11.2).ish del(Y)(SRY-) karyotype diagnosed by classical cytogenetics and fluorescence in situ hybridization (FISH). Ovarian tissue was full of oocytes and mitotic figures. FISH studies of ovarian tissues with X and Y centromere probes revealed extensive sex chromosome mosaicism, manifested by loss of the Y chromosome and polysomy of the X chromosome. We propose that X chromosome polysomy is a post-zygotic event that arises to facilitate gonadal differentiation in the absence of all factors necessary for normal gonadal development.     

8例性发育异常患者SRY基因分析

目的对8例性发育异常患者进行细胞遗传学及分子遗传学检查以探讨性别发育异常与SRY基因关系.方法用PY3.4,X着丝粒,SRY特异探针进行荧光原位杂交,用于分析性发育异常病人Y染色体及SRY基因异位情况.聚合酶链反应(PCR)扩增SRY基因,直接测序检测SRY基因突变.结果 2例46,XX男性,1例46,XY女性,1例45,X/46,XY嵌合体及1例46,X,t(Y;Y)(p11;q11)男性患者SRY基因均为阳性,直接测序未发现SRY基因阳性患者该基因突变.剩余1例46,XX男性,1例46,XY男性及1例46,XY女性患者SRY基因为阴性.FISH技术证实2例46,XX且SRY基因阳性的男性患者SRY基因易位至X染色体短臂末端.结论 SRY基因是人类性别决定的主导基因,但尚有其他基因参与性别分化.