Turner综合征122例核型与临床分析

本室自1982年～1999年对原发性闭经患者查出Turner综合征122例,核型多变,前3位者是45,XO(43例),45,XO/46,XX嵌合型(28例),46,X,i(Xq)(11例),临床表现主要是原发闭经和不孕.提示Turner综合征是引起原发性闭经最常见的染色体异常.     

96例Turner综合征患者临床特征及染色体分析

目的Turner综合征患者身材矮小伴不同程度的性腺发育不全,探讨Turner综合征不同核型的遗传学特征、临床特点及其所占比例。方法无菌取患者外周血,淋巴细胞常规培养制作染色体标本,胰酶法G显带,显微镜下进行染色体核型分析。结果96例Turner综合征患者的染色体核型为：45,x,39例（40．6％）;45,Ⅺ／46,XX21例（21．9％）;46,XY11例（11．5％）;46,Xi（Xq）10例（10．4％）;46,X,del（x）（q22。qter）6例（6．3％）;45,X／46,Xi（X）（q10;q10）3例（3．1％）;47,XXX3例（3．1％）;45,X／46,X,del（X）（022—pter）2例（2．1％）;45,Ⅺ／46,X,r（X）（p22q28）1例（1．04％）。结论Turner综合征患者的染色体有数目异常和结构畸变等多种核型,均可不同程度导致女性闭经、性腺发育异常及智力低下等症状,应提倡优生优育,做好产前诊断。     

大连地区78例Turner综合征的临床特征与染色体核型分析

目的探讨Turner综合征（TS）不同核型的遗传学特征、临床特点及其所占比例。方法成人外周血染色体核型分析,高危孕妇羊水染色体核型分析。结果成人外周血检测发现TS 75例,羊水检测发现TS 3例。78例患者中,45,XO 32例（41%）,45,XO/46,XX嵌合型10例（12.8%）,45,XO/46,XX/47,XXX嵌合型2例（2.6%）,45,XO/47,XXX嵌合型4例（5.1%）,46,X,i（X）4例（5.1%）,45,XO/46,X,i（X）嵌合型9例（11.5%）,46,X,del（Xp-）7例（9.0%）,46,X,del（Xq-）7例（9.0%）,45,XO/46,X,del（Xp11）嵌合型2例（2.6%）,45,XO/46,X,del（Xq21）嵌合型1例（1.3%）。结论 TS核型主要包括X单体型,X单体嵌合型和结构畸变型及其嵌合型三种,45,XO的X单体型为本综合症的主要类型;不同核型患者临床表现可存在差异;对有相关临床表现的女孩争取做到早诊断,早治疗;对部分具有一定生育能力的TS患者做好产前诊断,做到优生优育。     

临沂地区62例Turner综合征患者的细胞遗传学分析

目的 探讨临沂地区Turner综合征患者的染色体类型及与临床症状间的关系.方法 用1640培养基培养淋巴细胞,常规收获制片,G带显色(必要时加做C带显色),按人类细胞遗传学国际命名体制2005(ISCN2005)进行染色体核型分析.结果 62例Turner综合征患者检出染色体异常核型16种,包括:45,X、46,X,i(X)(q10)、45,X/46,XX、45,X/46,XY等,发现世界首报染色体异常核型1例.结论 临沂地区Turner综合征患者染色体的类型较多,临床表现差异较大.     

FISH技术在一例45,X/46,X,i（Xq）Turner综合征中的研究

目的应用荧光原位杂交技术（fluorescence in situ hybridization,FISH）分析一例45,X/46,X,i（Xq）嵌合体,并探讨其形成机理,临床表型与染色体核型的关系。方法通过染色体常规G显带技术,并联合FISH技术,选用X染色体着丝粒特异DNA探针（CSPX）和X染色体长臂全涂抹探针（Xq）,进一步确认异常染色体的来源。结果 G显带分析该患者染色体核型为45,X/46,X,i（Xq）,FISH技术证实了该异常染色体为Xq等臂染色体。结论 X短臂单体长臂三体型Turner综合征患者的临床表型与其染色体核型相关;在常规G显带的基础上,应用FISH技术可准确识别异常染色体,对明确诊断及后续治疗有指导意义。     

闭经与X染色体

本文对85例闭经患者进行细胞遗传学检查,其中原发性闭经68例,异常31例,占45.6％;继发性闭经17例,异常1例,占5.9％,均为X染色体结构和数目异常。卵巢性闭经是闭经的常见原因,而X染色体结构与数目畸变能影响卵巢的功能。31例原发性闭经染色体异常者中,45,X的11例,占16.2％、45,X/46,XX的11例,占16.2％、46,X,i(Xq)的7例,占10.2％、45,X/46,XY及46,XY各1例,占1.5％。继发性闭经1例异常者的核型为45,X/46,XX,其中45,X细胞系占4％。结合文献讨论了X染色体异常导致原发性闭经的原因,并对特殊病例的发病机制进行初步探讨。Xp,特别是Cen→Xp11(活性6区)及Xq27—28缺失导致典型Turner,这些患者大多性腺发育不全。Xp顶部(Xp21—22)及Xq13—缺失导致体矮及其它体征。Turner综合征患者的体征可有较大的变化,随正常细胞系的比例增多而逐渐减轻。     

Turner综合征的细胞遗传学、性激素与临床表型关系探讨

目的探讨Turner患者的染色体异常、性激素与临床表型的关系。方法对我院2012年1月以来68例Tuener综合征女性儿童患者进行外周血染色体核型分析和性激素检查。结果 68例Turner综合征患者,进行了外周血染色体核型分析检查,其中X染色体数目异常36例(52.94%),X染色体结构异常24例(35.29%),X染色体数目及结构均异常7例(10.29%),含Y染色体46,XY 1例(1.47%)。Turner患者的FSH明显高于正常对照组,E_2和P明显低于正常对照组,LH和RPL无明显差异。结论结合临床体征、染色体和性激素检查可以为Turner患者寻找病因提供理论依据,而且有利于指导治疗。     

羊水细胞荧光原位杂交技术及染色体核型分析在特纳综合征中的应用

目的探讨羊水细胞荧光原位杂交(fluorescence in situ hybridization,FISH)技术与染色体核型分析联合检测特纳(Turner)综合征,并结合产前超声筛查结果,评价FISH技术在产前诊断中的应用价值。方法对2010年1月至2012年12月来院产前遗传学诊断6455例孕妇,抽取羊水体外细胞培养后用常规G显带技术染色体核型分析为Turner综合征5例,正常对照2例,同时用FISH检测间期细胞13、18、21及X\Y的染色体数目。结果 Turner综合征5例中2例为染色体核型及FISH检测45,X,超声筛查结果异常;3例为染色体核型46,X,i(X)(q10),FISH检测正常,超声筛查结果异常;2例为染色体核型46,XX,FISH检测正常,超声筛查结果未见明显异常。结论 (1)FISH技术应用于产前诊断较常规核型分析方法有效缩短报告时间,但在Turner综合征染色体结构异常的患者,单纯使用FISH将发生漏诊。(2)FISH检测不能完全替代常规染色体核型分析,必须同时行羊水细胞染色体核型分析。     

应用荧光原位杂交技术对染色体病进行诊断

本文应用生物素标记的X -α着丝粒探针、特异区域单拷贝序列探针 2 1q2 2 .3;地高辛标记的重复序列探针pY3.4分别对 7例性腺发育不全、5例唐氏综合症患者外周血染色体及间期细胞核进行单色及双色荧光原位杂交 (FISH)。用染色体成像系统摄影并后期处理 ,显示的异常核型有 :45 ,XX/4 7,XXX ;45 ,XO/4 6 ,Xi(Xq) ;45 ,XO/4 6 ,XX ;47,XX 2 1;47,XY 2 1;47,XXY。中期分裂相FISH杂交结果与染色体G显带核型分析一致 ,间期细胞中荧光信号的数目与预期一致。     

117例原发性闭经患者的细胞遗传学分析

本文对117例原发性闭经患者进行静脉抗凝血染色体检查,发现染色体异常核型67例,异常发生率为57.27%(67/117),其中Turner综合征患者占异常核型的67.16%(45/67),46,XY核型7例,占染色体异常核型的10.44%(7/67)。原发性闭经表型正常患者50例,占受检总人数的42.73%(50/117)。本文对原发性闭经的细胞遗传学病因及异常核型与表型的关系进行了分析和讨论。     

Molecular diagnosis of Turner''s syndrome.

Turner's syndrome is a common disorder which occurs in around 1/3000 live births in girls. Diagnostic use of polymorphic DNA markers for the X chromosome could help to reduce the number of time consuming karyotype analyses needed. The M27 beta probe maps on the X chromosome to Xcen-Xp11-22 and in 83% of female subjects detects heterozygosity with multiallelic polymorphism. In Southern blotting, a single X chromosome yields a single hybridisation band. In this study, genomic DNA was extracted from leucocytes of 49 patients with Turner's syndrome (karyotypes: 45,XO, n = 29; 45,XO/46,XX, n = 4; 46,Xi(Xq), n = 1; 45,XO/46,Xi(Xq), n = 4; 45,XO/46,Xr(X), n = 4; 45,XO/46,XY, n = 4; 46,XXp-, n = 3), digested with EcoRI or HindIII, and analysed by Southern blotting. The molecular data for each patient were compared with DNA controls (homozygous 46,XX, heterozygous 46,XX and 46,XY DNA). A single band of reduced intensity compared to homozygous 46,XX control DNA was seen in 41 cases. Two hybridisation bands of different intensities were seen in four patients, in one of whom mosaicism was suspected on the basis of molecular analysis, despite a 45,XO karyotype. In four cases, Turner's syndrome failed to be detected: one 45,XO/46,XX mosaicism with only 4% of 45,XO cells and three distal Xp deletions. DNA analysis appears to be a useful and rapid tool in screening for Turner's syndrome and could be an alternative to cytogenetic analysis in diagnosing the disorder when severe growth retardation or delayed puberty are not accompanied by a Turner phenotype.     

Karyotype/phenotype correlation in females with short stature

We studied 60 females who presented with short stature. The main aim was to determine the effect of karyotype variation on phenotype. A somatic feature score was calculated for each case depending on the presence of 17 clinical somatic changes known to occur in Turner syndrome. Karyotype studies showed the following results: 45,X (n = 22): 46,XX (n = 11); 45,X/46,XX (n = 10); 46,XX/46,Xi(Xq) (n = 4); 46,XX/46,XXq- (n = 3); 46,XX/46,XXp- (n = 2); 46,Xi(Xq) (n = 2); 45,X/46,Xi(Xq) (n = 2); 46,XXp- (n = 1); 46,XX/47,XXX (n = 1); 46,XXq- (n = 1); 45,X/46,X(ry) (n = 1). Karyotype/phenotype correlation showed the gradation of severity of clinical phenotype to be related to the number of X chromosomes. The highest somatic scores and the most severe clinical manifestations were noted in cases of pure 45,X Turner and the mildest in 46,XX/46,XX(str) mosaics or pure 46,XX, including hypergonadotrophic hypogonadism. Our findings revealed a dosage effect of the X chromosome on phenotype, thus confirming that partial X chromosome inactivation modifies somatic and pubertal development. Our results also support both the additive and interactive hypotheses of karyotype/phenotype correlation.     

Chromosome abnormalities in a referred population for suspected chromosomal aberrations: a report of 4117 cases.

A cytogenetic study was performed on 4,117 Korean patients referred for suspected chromosomal abnormalities. Chromosome aberrations were identified in 17.5% of the referred cases. The most common autosomal abnormality was Down syndrome and Turner syndrome in abnormalities of sex chromosome. The proportions of different karyotypes in Down syndrome (trisomy 21 92.5%, translocation 5.1%, mosaic 2.4%) were similar to those reported in other countries. However, it was different in Turner syndrome (45, X 28.1%, mosaic 50.8%, 46, X, del (Xq) 4.4%, 46, X, i (Xq) 16.7%), in which proportions of mosaics and isochromosome, 46, X, i(Xq), were higher than those reported in other countries. In structural chromosome aberrations of autosome, translocation was the most common (43.6%), and duplication (21.3%), deletion (14.4%), marker chromosome (7.9%) and ring chromosome (4.0%) followed in order of frequency. Rates of several normal variant karyotypes were also described. Inversion of chromosome 9 was observed in 1.7% of total referred cases.     

Replication patterns of three isodicentric X chromosomes and an X isochromosome in human lymphocytes

Chromosomes from four patients with variants of the Turner syndrome were investigated by G- and C- banding and DNA replication techniques. Their karyotypes were: 1) 46,X,idic(X)(q28), 2) 45,X/46,X,idic(X)(q24), 3)45,X/ 46,X,idic(X)(p11), and 4) 46,X,i(Xq). In Patients 1, 2, and 3, the abnormal X was isodicentric, with different break-and-fusion points in each case. In each, the G-band pattern on one side of the breakpoint was a mirror image of that on the other side. Each had two distinct C-bands, only one of which was associated with a primary constriction. The fourth patient had an isochromosome of the long arm of an X in which only one C-band could be discerned. Replication studies were done on lymphocyte cultures by incorporating a thymidine analogue and staining with acridine orange. In addition, replication patterns of normal early- and late-replicating X chromosomes were studied in two normal females. In the four patients, all the normal X chromosomes had normal early-replication patterns. The two idic(X) chromosomes with break-and-fusion points on their long arms almost always had symmetric replication patterns, which demonstrates that the corresponding bands replicated synchronously. In contrast, many of the idic(X)(p11) and i(Xq) chromosomes showed asymmetric or asynchronous replication. In each, the replication pattern of the abnormal X was similar to the equivalent portions of a normal late-replicating X.     

7号染色体臂间倒位伴Turner综合征家系分析

目的研究7号染色体臂间倒位的遗传机制.方法患儿及父母作染色体检查,并对患儿的家系进行调查.结果患儿的染色体核型为46,XX,inv(7)(p22q11)/45,X,inv(7)(p22q11),其中46,XX,inv(7)(p2q11),85%,45,X,inv(7)(p22q11),15%.父亲的核型为46,XY,inv(7)(p22q11),母亲的染色体正常,患儿的母亲第1胎为3月自然流产,家系中其他成员均无流产史,母系成员中身材均偏矮小.结论染色体臂间倒位能引起流产和畸胎,应作产前诊断.     

Turner syndrome with rare karyotypes

Five cases of Turner syndrome with rare karyotypes are presented. The spectrum of chromosomal findings ranges from a female karyotype with a deletion of the short arm of one X chromosome, to a normal male karyotype. The following karyotypes were found: one case with 46,XXp--; two cases with 45,X/46,X,r(X); one case with 45,X/47,XYY; and one case with 46,XY.     

No evidence for chromosomal mosaicism in multiple tissues of 10 patients with 45 XO Turner syndrome

Why the frequency of spontaneous abortions among monosomy X conceptuses is 98 % while the postnatal course of Turner syndrome is relatively benign has not been understood. One explanation could be that mosaicism for a euploid cell line confers viability and that those 2 % of 45, XO zygotes surviving in utero have some degree of mosaicism. We thus reasoned that if the non-mosaic 45, XO karyotype is lethal, a thorough study of living Turner syndrome patients might reveal a much higher frequency of mosaicism than the 30–40 % reported. Ten adult women with a 45 , XO leukocyte karyotype were investigated, looking at five tissue types from all three germ layers: buccal mucosa and hair from ectoderm, urinary epithelium from endoderm and ectoderm, and lymphocytes and skin fibroblasts from mesoderm. We were unable to confirm mosaicism in these patients, although in 2 out of 10 there was the suggestion of a small percentage of euploid cells in skin and blood karyotypes.     

广州地区176例闭经患者的细胞遗传学分析

目的探讨细胞遗传水平上原发性闭经和继发性闭经患者的发病机理。方法 156例原发性闭经患者,20例继发性闭经患者的外周血进行培养、制片、烘烤、胰酶消化和染色。每例标本观察20个核型,分析3～5个核型。如果遇到嵌合体,观察100例。结果在176例患者中,检测出48例染色体核型异常患者,异常核型率为27.27%,主要为X染色体数目异常和45,XO嵌合体,包括14例45,XO,19例45,XO嵌合体,5例X染色体结构异常,6例46,XY。156例原发性闭经患者中检测出46例异常核型,而在20例继发性闭经患者中检测出2例异常核型。结论染色体异常是引起原发性闭经和继发性闭经的重要原因,对闭经病人进行染色体检测对确定其病因和治疗是必要的。