52例原发性闭经患者的细胞遗传学及临床特征分析

目的通过分析原发性闭经患者的细胞遗传学及临床特征,探讨原发性闭经与染色体异常的关系。方法对2014年10月至2016年3月在江苏省人民医院妇科门诊就诊的52例原发性闭经患者进行染色体核型及临床特征分析。结果 52例原发性闭经患者中染色体核型正常(46,XX)者27例,占51.92%(27/52);核型异常者25例,占48.08%(25/52)。25例异常核型中,性染色体异常21例(84.00%,主要为45,XO、45,X嵌合体和46,XY),常染色体异常4例(16.00%)。临床诊断为特纳综合征(Turner’s综合征,16例)、46,XY单纯性腺发育不全(Swyer’s综合征,5例)、苗勒管发育不全综合征(MRKH综合征,8例)、嗅觉缺失综合征(Kallmann’s综合征,4例)、特发性低促性腺激素性腺功能减退症(IHH,15例)和常染色体异常(4例)。结论染色体异常是原发性闭经的重要病因之一,其中性染色体异常最常见,包括Turner’s综合征和Swyer’s综合征,而MRKH综合征、Kallmann’s综合征以及IHH患者的核型正常。因此对原发性闭经患者常规进行染色体核型检查重要且必要,早期行病因诊断,可为下一步临床诊治提供依据。     

高通量基因测序技术在自然流产遗传学分析中的应用

目的初步探讨高通量测序技术在自然流产绒毛遗传学分析准确性和异常核型检出率中的作用。方法采用高通量测序和生物信息分析技术,选取常规染色体核型分析结果为46,XY的自然流产绒毛样本进行检测,比较两种检测结果的一致性及差异。结果 (1)常规染色体核型分析技术:14例样本染色体核型分析结果均为46,XY。(2)高通量测序技术:14例样本染色体核型均为46,XY,有拷贝数变异(CNV)改变的占43%(6/14),能检测到250kb~16.5M染色体片段的改变。(3)通过两种检测方法的比较,发现高通量测序技术检测时间短,对染色体结构异常有更高的检出率。结论高通量测序技术更敏感、高效,具有更高的染色体异常检出率。可作为常规染色体核型分析的补充检测手段。     

45,X/46,XY染色体嵌合体2例临床特点分析

正外周血染色体核型异常和Y染色体AZF基因缺失是引起男性不育的重要原因,患者多表现为无精子症、少精子症及性分化异常等[1]。染色体异常中45,X/46,XY嵌合体属性染色体发育异常,在不孕不育患者中有较高的发生率。45,X/46,XY嵌合体表现特征复杂,对患者性别、性腺发育及生育方面存在较大的影响,因此,对于45,X/46,XY嵌合体临床表型及细胞遗传学分析有助于诊断病因,并为后期治疗提供合理的指导方案。本文报道2例外周血染色体Tunner综合征和正常男性核型嵌合,且合并Y染色体AZF基因b和     

51057例患者外周血染色体核型与生殖异常关系的研究

目的 对51 057例生殖异常患者进行外周血染色体核型分析，探讨染色体核型异常类型与生殖异常之间的关系。方法 收集2005年1月至2021年7月于我院就诊的51 057例生殖异常患者为研究对象，抽取外周血进行淋巴细胞培养，行常规染色体制片及G显带染色体核型分析。根据染色体数目异常和结构异常等分类方法分别统计，分析不同染色体异常核型与生殖异常之间的关系。结果 共检出768例染色体核型异常患者(不包括染色体多态性),检出率为1.50%。常染色体异常共348例，占染色体异常核型的45.31%,检出率为0.68%;性染色体异常400例，占染色体异常核型的52.08%,检出率为0.78%;性反转共20例，占染色体异常核型的2.60%,检出率0.04%。共检出染色体多态性改变2 274例，检出率约为4.45%。结论 染色体异常是导致不孕不育等生殖异常的重要遗传因素之一，进行常规染色体核型分析有助于明确病因，并及时进行遗传咨询，以采取合理的干预措施。     

尿道下裂患儿细胞遗传学特点分析

目的探讨尿道下裂患儿的细胞遗传学特点。方法回顾性分析2008年6月至2018年5月于天津市儿童医院就诊的45例有细胞遗传学异常的尿道下裂患儿的临床资料。中位年龄为10个月(3 h~5岁)。45例中20例为近端型尿道下裂,1例为中段型尿道下裂;24例合并不同程度的泌尿生殖系统畸形,其中15例合并单侧或双侧隐睾,5例阴囊分裂,3例阴茎阴囊转位,3例小阴茎,3例合并腹股沟斜疝,1例重复尿道,1例鞘膜积液,1例隐匿阴茎。在合并其他系统畸形方面,1例合并唇腭裂,1例合并先天性心脏病。患儿均行外周血淋巴细胞G显带染色体核型分析,分析患儿的细胞遗传学特点。结果45例中,性染色体异常28例(62.22%),包括47,XXY、46,XX/47,XXY、45,X0/47,XYY等核型;性反转8例(17.78%),均为46,XX;常染色体异常4例(8.89%),包括46,XY,9p+、46,XY,10p+和46,XY,1q+;染色体多态性4例(8.89%),包括46,XY,inv(9)和46,XY,16qh+;平衡易位1例(2.22%),为45,XY,-21,-22,+t(21;22)。45例中8例染色体核型为46,XX的尿道下裂患儿,即性反转患儿,均为近端型尿道下裂。结论尿道下裂患儿可合并染色体核型异常,包括性染色体异常、常染色体异常、染色体多态性及染色体平衡易位,其中性染色体异常最多见,平衡易位最少见。     

男性儿童常见外生殖器畸形的异常染色体核型特点

目的探讨男性儿童常见外生殖器畸形的异常染色体核型特点。方法回顾性分析2012年1月至2017年12月浙江大学医学院附属儿童医院收治的2 408例患儿的临床资料。平均年龄(38±7)个月。其中尿道下裂1 115例, 隐睾189例, 小阴茎304例, 隐匿性阴茎681例, 性发育异常119例。所有患儿均行外周血染色体550带检测, 并分析染色体的核型。结果本组2 408例, 共检测出异常染色体核型131例, 检出率5.4%, 其中染色体数量异常46例, 结构异常85例;性染色体异常64例, 常染色体异常67例。最常见的异常染色体核型为46, XY, inv(9)(p12q13), 共28例, 占比21.4%;其次为47, XXY, 共16例, 占比12.2%。性发育异常、尿道下裂、隐睾、小阴茎、隐匿性阴茎患儿染色体异常检出率分别为12.6%(15例)、5.5%(61例)、5.3%(10例)、4.9%(15例)、4.4%(30例)。结论男性常见外生殖器畸形患儿中染色体异常不罕见。染色体结构异常较数量异常更常见, 性染色体异常与常染色体异常占比相当。     

继发闭经染色体异常一例

<正> 1990年6月为一例继发性闭经患者作外周血染色体检查,其结果为异常染色体核型。1992年9月经湖南医科大学医学遗传室国家培训中心夏家辉教授鉴定为世界首报核型,现报告如下。患者25岁,已婚,原发不孕,因继发闭经4年余,于1990年6月就诊于我院妇科门诊,经有关检查,确诊为高促性腺激素性闭经,后作外周血染色体     

外生殖器畸形患者遗传学检查的临床意义

目的 探讨遗传学检查在生殖器发育畸形患者临床诊断和治疗中的作用.方法 收集20例不同程度外阴发育异常患者的外周血,运用G显带技术进行染色体核型分析,PCR技术检测SRY基因(sex-determining region of Y chromosome,SRY).结果 6例真两性畸形的核型为46,XX;45,X;46,XX/46;XY和46,XX/47,XXY,其中1例46,XX个体的SRY(-),其余5例SRY(+);6例男性假两性畸形,存在睾丸组织,核型均为46,XY,且SRY(+);2例女性假两性畸形,具子宫及卵巢,核型46,XX,SRY(-);1例46,XY女性综合征,具子宫及双侧卵巢间质,核型46,XY,SRY(-);1例46,XX男性综合征,隐睾,核型46,XX,SRY(+);3例母孕期药物影响女婴,具子宫及卵巢,核型46,XX,SRY(-);1例肥胖引起的埋藏阴茎,核型46,XY,SRY(+).结论 临床上对生殖器发育畸形患者进行核型分析和SRY基因检测,有利于早期对性腺发育的判断,促进疾病的诊断和治疗.妇女孕期性激素的使用应加强管理.     

雄激素不敏感综合征临床诊治分析（附6例报告）

目的：探讨雄激素不敏感综合征（androgen insensitivity syndrome,AIS）患者临床诊断和治疗方法,提高对AIS的诊治效率。方法：回顾性分析我院1985年9月~2012年6月收治6例AIS患者的临床特征,诊断与处理。所有患者均进行了染色体,性激素六项,下腹部B超,术中切除组织病理检测等检查,其中5例患者给予手术切除性腺组织,术后给予小剂量雌激素治疗,1例给予保守治疗。结果：AIS患者多以原发闭经就诊,染色体核型均为46,XY。性激素六项中除了睾酮和LH升高外,其余项未见明显异常。术中切除组织病理检查提示睾丸间质细胞和支持细胞组成的正常睾丸组织,未发现睾丸肿瘤。所有手术患者均未出现女性第二性征发育停滞及骨质疏松等性腺切除后并发症。结论：AIS患者多以“原发闭经就诊”,染色体核型分析联合下腹部B超检查均能有助于AIS快速检出,手术切除性腺具有安全行和可行性。同时加强AIS遗传病史家族胎儿染色体筛查有重要意义。     

羊水间期细胞荧光原位杂交检测残余风险评估:6125例产前细胞遗传学诊断回顾性分析

目的评估中孕期羊水间期细胞荧光原位杂交(FISH)检测之后漏诊非13、18、21、X、Y染色体的非整倍体异常核型的残余风险,从产前咨询的角度来评价间期FISH检测在产前诊断中的作用。方法对6 125例中孕期羊水传统核型分析的结果进行回顾性分析,假设这些病例均进行间期FISH检测,计算在三大产前诊断指征(孕妇高龄、孕母血清学筛查18-三体或21-三体高风险、妊娠23周前超声发现胎儿有结构异常)情况下间期FISH检测的检出率以及残余风险。结果从2011年1月至2014年9月共有6 125例单胎孕妇行中孕期羊水细胞核型分析,共检出207例(3.38%)异常核型。有161例(77.8%)为涉及13、18、21、X、Y染色体非整倍体的异常核型(包括嵌合体),其间期FISH检测结果为阳性。有46例(22.2%)异常结果是非13、18、21、X、Y染色体的非整倍体,其中包括平衡性结构重排31例(67.4%)、非平衡性结构重排14例(30.4%)、其他染色体非整倍体1例(2.2%)。在这46例异常核型中,有6例涉及21号染色体和1例涉及13号染色体的不平衡性重排的间期FISH检测结果为阳性,其余39例间期FISH检测结果均为阴性。计算间期FISH检测的检出率为81.2%(168/207),间期FISH检测的残余风险为0.65%(39/5957)。结论间期FISH检测是核型分析的有效补充,但不能取代核型,单纯行间期FISH检测进行产前诊断会漏诊约18.8%的染色体异常。在产前遗传咨询时应向病人解释间期FISH的检出率和残余风险,了解间期FISH的优点和局限性,帮助其选择合适的产前诊断手段。     

Cytogenetic analysis of patients with amenorrhea

Objective: To analyse the cytogenetic examination results and investigate the effect of chromosome abnormalities on amenorrhea.Methods: The routine cytogenetic analysis was performed, including the chromosome G band analysis and karyotype analysis of the cultured peripheral blood lymphocytes from the patients with primary amenorrhea or secondary amenorrhea.Results: One hundred and thirty-seven cases were found with chromosome abnormalities in 234 patients with primary amenorrhea. The incidence of chromosome abnormality was 58.6%. In 309 with secondary amenorrhea, the incidence of chromosome abnormality was 13.6%.The reported abnormalities included the numerical and structural abnormalities of X chromosome, 46,XY, 45,X0/46,XY,and the structural abnormality of autosome.Conclusions: Chromosome abnormality is one of the main causes of amenorrhea. Karyotype analysis of chromosome is absolutely necessary for the diagnosis and treatment of patient with amenorrhea.     

Cytogenetic investigation of 468 patients with primary amenorrhea

<正>Objective:To analyze the relationship between karyotypes and clinic features of patients with primary amenorrhea. Method:G-banding was employed in karyotype analysis of patients with primary amenorrhea. Results:Karyotype analysis of 468 patients with primary amenorrhea revealed that 255 patients(54.49%) had normal female karyotypes and 213 patients(45.41%) had abnormal karyotypes,including 143 patients with abnormal X chromosome,4 patients with mosaic X-Y chromosome,57 patients with 46,XY karyotype,8 patients with abnormal autosome and one patient with X-autosome translocation.All primary amenorrhea patients with deletion or break-up in Xp11.1-11.4 were short in stature. Conclusion:One of the main reasons of primary amenorrhea was chromosome abnormalities,especially sex chromosome abnormalities.Karyotype analysis should be routinely applied to detect primary amenorrhea patients. Xp11-12 may be critical to development of stature.     

45,X/ 46,XX/ 46,XY Mosaic with female phenotype]

Report on a girl with female phenotype and 45,X/46,XX/46,XY mosaicism. The patient showed primary amenorrhea, low stature (1,47 m), but no other typical features of Turner's syndrome. Chromosome studies were carried out on cultures of blood lymphocytes, with usual methods and with R- G- and Q-banding: 43,3 % of cells were 46,XY ; 36,6 % were 45,X and 20 % were 46,XX. The chromosome Y is a non-fluorescent one. A comparison is made with other published cases.     

Clinical aspects of 49 infertile males with 45,X/46,XY mosaicism karyotype: A case series

Disorders of sex development (DSD) are congenital abnormalities as an atypical development process in either gonadal or chromosomal structure. It is the cause of the abnormality in phenotype and characteristics. Chromosomal analysis plays an important role in the DSD determination. 45,X/46,XY mosaicism is a rare karyotype, and its prevalence is about 1.5 in 10,000 newborns. It affects the growth, hormonal balance, gonad development and histology. All data such as height, male general appearance, testis size and volume, external genitalia, spermogram and hormonal levels, testis pathology, Y chromosome microdeletion and karyotype, and assisted reproductive technology (ART) outcome were recorded based on patients profile and history. We investigated 64 infertile males with 45,X/46,XY mosaicism. Fifteen cases who had structural abnormalities in Y chromosome were excluded. From 49 available spermogram, 21 cases reported as azoospermic men, while 28 of them classified as nonazoospermic patients in which four of them displayed normal spermogram. According to hormonal evaluation, there were no significant differences between azoospermic and nonazoospermic groups. In azoospermia, only three couples underwent an ART cycle in which all of them failed. From 14 nonazoospermic cases who entered into the ART cycle, three cases experienced a successful pregnancy that one of the prosperous outcomes was twins. In 45,X/46,XY cases, both 45,X and 46,XY cell lines are seen. Various distributions of both cell lines can reflect a wide range of phenotypes that may be the most comprehensive evaluation in infertile males with 45,X/46,XY karyotype. It assumes that karyotyping as a main diagnostic test can enable us to find these rare cases.     

Chromosomal abnormalities in 2 cases of testicular failure

This study investigated the underlying chromosomal abnormalities of testicular failure using molecular cytogenetic analysis. We report 2 cases of rare genetic anomalies that resulted in hypogonadism. The first patient presented with severe hypogonadism. Chromosome analysis revealed a mosaic 46,X,r(Y) (p11.3q11.23)/45,X karyotype, with a ring Y chromosome. A Y chromosome microdeletion assay showed a deletion in the azoospermia factor a region. The second patient presented with infertility and nonobstructive azoospermia. Cytogenetic and fluorescent in situ hybridization analysis revealed a 47,XY,+mar.ish i(15) (D15Z1++,SNRPN2,PML2) karyotype, with a small supernumerary chromosome derived from chromosome 15. These results emphasize the need for molecular cytogenetic evaluation in patients with testicular failure before using advanced reproductive techniques.     

Detection of chromosomal abnormality and Y chromosome microdeletion in patients with azoospermia and oligozoospermia

Objective:To investigate the chromosomal abnormality and Y chromosome microdeletion in patients with azoospermia and oligozoospermia.Methods:Cytogenetic karyotype analysis and multiplex PCR were used to detect chromosomal abnormality and Y chromosome microdeletion in 99 azoospermic and 57 oligospermic patients(total 156).45 fertile men were includ-ed as controls.Results:31 patients were found with chromosomal abnormalities in 156 cases(31/156,19.9 %),20 cases showed 47,XXY,2 cases showed 46,XY/47,XXY,7 cases had Y chromosome structural abnormalities and 2 had autosomal chromosome abnormalities.There were significant differences between the frequency of AZF microde-letion in 125 cases with normal karyotype and 45 controls(P<0.01).The frequency of AZF microdeletion in 68 azoospermic and 57 oligospermic patients were 14.7%(10/68)and 15.8%(9/57)respectively,the difference was not significant(P>0.05).AZFa,AZFb,AZFa+b,AZFb+c,AZFa+b+d and AZFb+c+d mierodeletions were found in azoospermic patients.AZFb,AZFc,AZFd,AZFb+c+d and AZFc+d microdeletions were found in oligo-spermic patients.Conxlusion:The frequency of chromosomal abnormality was 19.9% and the frequency of Y chromosome mi-crodeletion was 15.2% in patient with azoospermia and oligozoospermia.We should pay close attention to this prob-lem.     

男性不育症中染色体特殊核型

在男性不育症的遗传咨询门诊中，发现的染色体异常绝大多数为典型的４７，ＸＸＹＫｌｉｎｅｆｅｌｔｅｒ综合征，但我们也发现一些较为特殊的核型，其中多Ｘ及多Ｘ嵌合体的３例，Ｙ染色体结构异常及Ｙ染色体与常染色体易位２例；常染色体之间的平衡易位６例。本文讨论了染色体的异常与男性不育症之间的可能关系。     

Chromosomal abnormalities in patients with azoospermia in Western Mexico

In order to assess the frequency of chromosomal abnormalities in azoospermic males from western Mexico, we carried out a retrospective study in 227 patients. Forty-three (18.9%) cases with an abnormal karyotype were found. The most frequent chromosomal anomaly was 47,XXY, which was identified in 35 subjects (15.4%). In six cases (2.6%), structural aberrations were detected: two Robertsonian translocations [(45,XY,t(13;22)(p11;p11) and (45,XY,t(13;15)(p11;p11)], a Y;autosome translocation [46,XY,der(15)t(Y;15)(q12;p11)], and three mosaics [mos45,X/46,X,idic(Y)(q11)]. In general, these findings are in accordance with those from other surveys and confirm that the XXY aneuploidy is the most frequent chromosomal abnormality in azoospermic individuals.     

A familial analysis of two brothers with azoospermia caused by maternal 46,Y,t(X; 1) (q28; q21) chromosomal abnormality

Chromosomal abnormality is a primary genetic factor that lead to azoospermia and male infertility. Here, we report the cases of two brothers with primary infertility, whose chromosomes displayed a balanced translocation, and their karyotypes were 46,Y, t(X; 1) (q28; q21). Both presented an azoospermia phenotype without abnormal clinical symptoms. Their mother's karyotype was 46,X, t(X; 1) (q28; q21), and their father's chromosome karyotype was 46,XY. No abnormal changes were noted in the copy number of chromosome fragments in the whole genome. This study is the first to report showing that 46,Y, t(X; 1) (q28; q21) chromosomal abnormalities are associated with azoospermia.