染色体平衡易位患者精子染色体荧光原位杂交分析

目的:探讨外周血染色体平衡易位患者在精子发生过程中染色体分离模式,了解各分离模式产生精子所占比例,预测染色体平衡易位携带者在胚胎移植前遗传学诊断(PGD)中得到正常表型胚胎的概率,评估其进行PGD的风险。方法:应用三色荧光原位杂交(FISH)对4例染色体平衡易位患者46,XY,t(9;11)(q22;q21)、46,XY,t(11;22)(q23;q11)、45,XY,t(13q;15q)、45,XY,t(13q;14q)进行精子相关染色体分析,计算出各染色体分离模式产生精子所占比例,同时以染色体正常男性的正常精液作为对照。结果:上述4例异常精子所占比例分别为50.86%、58.33%、13.00%和22.82%,均明显高于对照组(0.85%、1.63%、1.60%和1.37%)。结论:通过FISH检测染色体平衡易位患者精子染色体,有助于预测染色体平衡易位携带者在PGD过程中的风险,从而选择应用PGD。     

1个Y染色体微缺失合并19号染色体臂间倒位的家系分析

目的:对1个男性不育家系进行细胞和分子遗传学分析。方法:分析不育家系中3例男性的临床症状,并采用染色体核型分析、序列标签位点-PCR(STS-PCR)和多重连接依赖探针扩增(MLPA)等方法进行检测。结果:先证者及其哥哥的染色体核型为46,XY,inv(19)(p13.3q13.1),其父亲为46,XY;3例男性均为Y染色体AZFc区缺失携带者,MLPA检测发现三者在AZFb、AZFc区有相同的基因拷贝数的减少。结论:联合应用核型分析、Y染色体STS-PCR和MLPA等多种方法,揭示了1个男性不育家系的遗传学病因。     

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     

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。     

三代旁系血亲婚育子代男性不育临床及细胞分子遗传学研究

目的探讨三代旁系血亲婚育子代与男性不育的关系及其细胞分子遗传学特征。方法回顾性分析3例三代旁系血亲婚育子代男性不育的临床特点,并对其外周血淋巴细胞染色体核型及Y染色体微缺失进行检测分析。结果 3例三代旁系血亲子代分别为严重少弱畸精子症和无精子症,查体双侧睾丸大小均正常,无精索静脉曲张。血清性激素水平均正常。染色体核型同为46,XY,Y染色体数目及结构无异常,Y染色体微缺失筛查未发现缺失。结论三代旁系血亲结婚增加子代的不育风险,可能与父母近亲结婚增加隐性致病基因的纯和概率及基因变异有关。     

7例45,X/46,XY嵌合型性腺发育不全患者临床报告

<正>45,X/46,XY为性腺发育不全的一种疾病,其发生机制可能与Y染色体微缺失、Y染色体性别决定基因(SRY)或其他性别决定基因发生突变或调节异常有关,临床表现为从女性生殖器模糊到男性无精子症等一系列临床表型[1]。外周血染色体核型嵌合体细胞比例与临床表现之间无相关性,嵌合型45,X/46,XY在文献中很少报道患者具有生育能力[2-3],本文报道7例45,X/46,XY嵌合型性腺发育     

Y染色体异态与临床关系的探讨

Y染色体异态是否能造成临床效应而导致疾病,一直有争议。有人认为大Y属染色体遗传多态性,无临床意义。近年来有研究提示大Y是来自异染色质中DNA过多的重复,从而引发某些临床症状,如男性不育及胎儿发育异常[1]。作者对189例男性不育患者做Y染色体检查,并对大Y染色体携带者与不良孕产史之间的关系进行分析探讨。 资料与方法 1.临床资科 189例男性不育患者均来源于     

性分化异常病人SRY基因检测的临床意义

目的：为探讨Y染色体上性别决定区基因（SRY）在性分化中的作用。方法：在染色体核型分析的基础上，应用聚合酶链反应（PCR）对4例性分化异常的病人进行SRY检测、结果：2例46，XX男性中1例SRY阳性，1例SRY阴性．2例46，XY女性SRY阳性。结论：SRY基因检测在性分化异常的诊断中有重要意义，但性别决定是一个复杂的过程，不排除还有除SRY以外的遗传机制参与。     

闭经患者的细胞遗传学分析

目的分析闭经患者细胞遗传学的检查结果,探讨染色体异常对性腺发育及表型的影响。方法对234例原发闭经和309例继发闭经患者进行外周血染色体的核型分析。结果原发闭经患者染色体异常137例,异常检出率为58.6%;继发闭经患者染色体异常42例,异常检出率为13.6%。染色体异常包括X染色体数目及结构异常,46,XY、45,X0/46,XY以及常染色体结构异常。结论染色体异常是闭经的主要原因之一,染色体核型分析对闭经患者的诊断和治疗是必要的。     

染色体变异对男性生育能力影响的分析

目的探讨染色体的异常对男性生育能力的影响。方法对男性不育就诊的4183例男性患者进行G显带核型分析。结果1097例染色体异常核型中,常染色体数目异常占1．73%(19/1097)；常染色体结构异常13．49% (148/1097)；性染色体数目异常占30．08%(330/1097)；性染色体结构异常例占53．24%(584/1097)；嵌合体占1．46%(16/1097)。结论染色体变异对男性生育有重要影响。对于睾丸发育不良、畸形精子多、少精子、无精子以及其妻有反复流产史、死胎史和畸胎史的男性患者应进行染色体检查,以排除染色体畸变的可能。     

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。     

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.     

Cytogenetic studies in Balkan endemic nephropathy

The G band characteristic of chromosomes in 15 patients with Balkan endemic nephropathy (BEN), 20 relatives with no features of the disease and 25 healthy controls were investigated by cytogenetic analysis of lymphocyte cultures from peripheral blood. A specific chromosome marker in BEN was established in one No. 3 chromosome homologue characterized by a discordance in the banding patterns of the long arm, shortening the band 3q25 with faster fusion of subbands q26.1 and q26.3, and lack of differentiation of q24. Among the patients there were a mosaic case with a caryotype: 46,XY/46,XY,t(1;3) (q11.2;q25) and another one with a t(2;3)(p11.2; q25) in a tetraploid lymphocyte cell. The evidence of shortening of q25 and postzygotic mutations for 1/3 translocation and 2/3 translocation with the breakpoints on chromosome 3 being in 3q25 suggested that the critical band for BEN is 3q25.     

Sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility

In this report, we present the overall sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility. The study consisted of 40 patients with a control group of 55 infertile non-azoospermic males with a normal 46,XY karyotype who visited the Reproduction Center of Toho University Hospital during the 5.5-year period between January 1991 and June 1996 with the chief complaint of male infertility. Among the 40 patients with Klinefelter's syndrome, 38 cases were pure 47,XXY, one case was 47,XXY with a pericentric inversion of chromosome 9 and one case was a mosaic of 46,XY/47,XXY(2:28). Thirty-nine of these 40 patients were azoospermic and one (47,XXY) had severe oligoasthenozoospermia. The sexual function of the patients was evaluated according to their responses to a preliminary questionnaire devised by our department. There was no significant difference in the frequency of sexual function disturbances between the patients with Klinefelter's syndrome and the control group (67.5% vs. 60.0%; χ² analysis; p = 0.454). The mean frequency of sexual intercourse per month in the patients with Klinefelter's syndrome was significantly higher than in the control group (4.4 ± 2.8 vs. 3.3 ± 1.6: Welch's t -test, p < 0.05). A possible explanation for this variation may lie in the fact that many of these patients were diagnosed with azoospermia prior to the administration of the questionnaire and may have wished to continue to have relations as a couple.     

精子荧光原位杂交分析男性臂间倒位携带者的减数分裂结果

目的:探讨用精子荧光原位杂交(fluorescence in situ hybridization,FISH)分析男性染色体臂间倒位携带者的减数分裂结果。方法:对4例男性染色体臂间倒位携带者的精子通过化学方法解聚,利用双色FISH,分析精子染色体组成并推断其分离类型。结果:4例染色体臂间倒位携带者中2例为46,XY,inv(9)(p11q12),1例为46,XY,inv(9)(p11q13),1例为46,XY,inv(6)(p22q24),其倒位片段长度分别占整条染色体的16.0%、16.0%、21.0%和76.0%,其重组精子分别为0.2%、0.4%、0.3%和43.9%(del(p)/dup(q)占22.4﹪,del(q)/dup(p)占21.5﹪)。结论:染色体臂间倒位携带者减数分裂的重组发生跟倒位片段占整条染色体长度比例有关。FISH分析可了解重组后染色体不平衡精子的比率,有助于提供更准确的遗传咨询。     

应用SRY基因检测性发育异常的研究

性分化异常与Ｙ染色体有直接的联系，而睾丸的发生与Ｙ染色体短臂上１Ａ１Ａ性别决定区（ＳＲＹ）基因密切相关。本文对表型男性的４６，ＸＸ和表型女性的４６，ＸＹ、４５，Ｘ／４６，Ｘ，ｔ（Ｙ；Ｙ）、４６，ＸＹ，表型女性盆腔肿瘤、４６，ＸＹ，外生殖器官及性腺发育异常、Ｘ染色体与常染色体易位的原发闭经等六个类型１６例病人应用ＰＣＲ技术进行ＳＲＹ基因的体外扩增检测。结果１２例ＳＲＹ阳性，４例ＳＲＹ阴性，为临床诊断治疗提供了依据。     

A novel mutation in steroidogenic factor (SF1/NR5A1) gene in a patient with 46 XY DSD without adrenal insufficiency

Steroidogenic factor‐1 (SF‐1), also known as nuclear receptor subfamily 5 group A member 1 (NR5A1), is a member of orphan receptor subfamily and located on chromosome 9 (9q33). In 46, XY individuals with mutation of SF‐1 gene, adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus, infertility can occur from severe to mild. We report a case of a 20‐day‐old male who is admitted to our clinic due to ambiguous genitalia. In this report, we describe a novel heterozygous c.814A > C (p. T272P) NR5A1 mutation in a patient with 46, XY DSD without adrenal insufficiency. We describe a novel missense mutation c.814A > C (p. T272P) in NR5A1 gene which had not previously been reported. Also this report highlights that the potential diagnostic utility of next‐generation sequencing is an effective strategy versus Sanger sequencing to identify genetic mosaicism in clinical practice.     

Cytogenetic aberrations in perineurioma: variation with subtype

Only two karyotypes of perineurioma have previously been reported, 46XX,del(10)(q22q24),der(10),del(22)(q11-12q?)/47, idem,+der(10) (in a sclerosing perineurioma of the finger) and 45,XX,add(14)(p13),-22,add(22)(q11.2) (in an intraneural perineurioma). We investigated the clinicopathologic and cytogenetic findings in four consecutive perineuriomas in children, including two small (< or =1 cm) digital sclerosing perineuriomas, a 2-cm intraneural perineurioma, and a 16-cm abdominal soft tissue perineurioma. All lesions showed plump perineurial cells in a complex whorled configuration. Immunohistochemical (strong EMA immunostaining in all cases) and ultrastructural (in three of three lesions examined) evidence of perineurial differentiation was present. The sclerosing perineuriomas showed 46,XY,t(2;10)(p23;q24) and 47,XX,add(3)(q23),add(6)(q21),-5,-9,-10,-22,+mar1,+mar2,+mars; the intraneural tumor showed 46,XX,add(2)(q11.2),add(3)(q12); and the abdominal soft tissue perineurioma showed 46,XX,t(8;9)(q13;q22). Metaphase FISH analysis for an ALK gene rearrangement in the sclerosing perineurioma with t(2;10) was negative; the ALK signal remained on the der(2). We conclude that perineuriomas display mostly simple karyotypes, characterized by one or few chromosomal rearrangements or numerical changes. In conjunction with the previously published sclerosing perineurioma karyotypes, the findings of chromosome 10 aberrations, t(2;10)(p23;q24) and monosomy 10 in two sclerosing perineuriomas, indicate that rearrangements and/or deletions of 10q are a consistent finding in this variant of perineurioma. The findings also expand previous assertions that chromosome 22 abnormalities are pathogenetic in perineurioma and suggest that diverse genetic tumorigenic mechanisms may exist, possibly depending on the subtype.