Mucinous cystadenoma in a female patient with 45,X/46,XY karyotype

The mosaic karyotype of 45,X/46,XY has a wide phenotypic spectrum and there are substantial differences between prenatally and postnatally diagnosed cases. The phenotype varies between normal male to classical Turner syndrome. There is a high risk of gonadal tumor development in the dysgenetic gonads of patients with sex chromosome mosaicism. We report a case of a 24-year-old patient with a pelvic mass and amenorrhea referred to our laboratory for karyotyping. Peripheral blood chromosome analysis showed a mosaic karyotype of 45,X[17]/46,XY[83]. The tumor originated from the left ovary and the right ovary was found to be a streak gonad. The uterus was intact. Pathologic examination of the tumor revealed mucinous cystadenoma. Physical examination of the patient showed signs of Turner syndrome, as short stature (145 cm), short neck and asymmetric shoulders. Her mental state was normal. Y chromosome microdeletion screening involving SRY and ZFY genes was performed and no deletion was found. The patient was informed about the condition during the genetic counseling session.     

Genetic evaluation of severe male factor infertility in Turkey: A cross-sectional study

Objective: To determine the frequency, types of chromosomal abnormalities and Y chromosome microdeletions in patients with severe male factor infertility, and the association between clinical background and genetic abnormality. Study design: A total of 322 infertile men; 136 men with severe oligozoospermia (sperm count <5 million/ml) and 196 with nonobstructive azoospermia were studied between April 2004 and November 2006 at the Dr. Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey. Blood, semen samples, and testicular biopsies of patients were obtained. Hormonal analysis (follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels), semen analysis, karyotype analysis, and PCR screening for Y chromosome microdeletions were performed. Result(s): Forty-eight out of 332 (14%) infertile men had a genetic abnormality. Twenty-four (7.2%) cases with karyotype abnormality were detected. The frequencies of karyotype abnormalities were Klinefelter’s syndrome 17/24 (71%), translocation 3/24 (12%), mix gonadal dysgenesis 2/24 (8%), XX male 1/24 (4%), and 46XYY 1/24 (4%). Twenty cases (6%) infertile men had only Y chromosome microdeletions. The frequencies of the deleted areas were azoospermia factor (AZF)c 42%, AZFb 25%, AZFa 21%, AZFb, c 8%, and AZFa, c 4%. Four of the cases with Y chromosome microdeletions also had a concurrent karyotype abnormality. Conclusion(s): All patients with nonobstructive azoospermia and severe oligozoospermia (sperm count <5 million/ml) should undergo genetic screening.     

Detection of mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes in a phenotypically normal male neonate with prenatally detected 45,X/46, XY at amniocentesis and cytogenetic discrepancy in various tissues

ObjectiveWe present detection of mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes in a phenotypically normal male neonate with prenatally detected 45,X/46, XY at amniocentesis and cytogenetic discrepancy in various tissues.Case reportA 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X [8]/46,XY [15]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed the result of arr (Y) × 0–1 with 25.493-Mb mosaic deletion of chromosome Yp11.31-q11.23. Prenatal ultrasound findings were unremarkable. The fetus had normal male external genitalia on fetal ultrasound. Following genetic counseling, the pregnancy was carried to 38 weeks of gestation, and a phenotypically normal male baby was delivered without any abnormalities of the male external genitalia. The cord blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[3]/46,XY [29], and placenta had a karyotypes of 45,X [25]/46,X,i(Y) (q10)[7]/46,XY [8]. When follow-up at age two months, the neonate was normal in development. The peripheral blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[5]/46,XY [27]. Interphase fluorescence in situ hybridization (FISH) analysis on 101 buccal mucosal cells showed normal X and Y signals in 101/101 cells.ConclusionFetuses with 45,X/46, XY at amniocentesis can be associated with mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes, cytogenetic discrepancy in various tissues and a favorable outcome.     

Scant XYqh- testicular cells with normal SRY was enough to differentiate bilateral testes in a 45,X/46,XYqh- patient

OBJECTIVE: It has been established that in 45,X/46,XY individuals predominance of XY or XO gonadal cells determines gonadal differentiation. However, in some cases there is no concordance between the predominance of XY cells and testis differentiation. Here we describe the SRY findings in a patient bearing a 45,X/46,XYqh- karyotype. STUDY DESIGN: The patient presented two small testes (one with spermatogenesis), a male phenotype, and a predominant 45,X karyotype in leukocytes and gonadal cells. PCRs of SRY, ZFY and Yqh were performed on DNA from leukocytes and from left gonadal tissue. SRY-PCR products were purified and sequenced. RESULTS: A normal SRY sequence was found in both tissues. CONCLUSIONS: Despite the predominance of 45,X cells in gonads, some patients in whom SRY is normal can develop testes, probably due to the presence of alternative mechanisms involved in testicular differentiation; however, further gonadal development could be impaired.     

Anomalies de structure du chromosome Y et syndrome de Turner

Although specifically male, the human Y chromosome may be observed in female karyotypes, mostly in women with Turner syndrome stigmata. In women with isolated gonadal dysgenesis but otherwise normal stature, the testis determining factor or SRY gene may have been removed from the Y chromosome or may be mutated. In other women with Turner syndrome, the karyotype is usually abnormal and shows a frequent 45,X/46,XY mosaicism. In these cases, the phenotype depends on the ratio between Y positive and 45,X cell lines in the body. When in mosaicism, Y chromosomes are likely to carry structural abnormalities which explain mitotic instability, such as the existence of two centromeres. Dicentric Y isochromosomes for the short arm (idic[Yp]) or ring Y chromosomes (r[Y]) are the most frequent abnormal Y chromosomes found in infertile patients and in Turner syndrome in mosaic with 45,X cells. Although monocentric, deleted Y chromosomes for the long arm and those carrying microdeletions in the AZF region are also instable and are frequently associated with a 45,X cell line. Management of infertile patients carrying such abnormal Y chromosomes must take into account the risk and the consequences of a mosaicism in the offspring.     

1例嵌合型45,X/46,X,r(Y)患者的遗传学分析

目的:应用细胞遗传学和分子生物学技术分析1例嵌合型45,X/46,X,r(Y)患者的核型。方法:应用常规染色体标本制备方法进行G-显带和C-显带;并应用CEPX(DXZ1,Xp11.1-q11.1,Spectrum Green,Vysis)探针、LSI SRY(Yp11.3,Spectrum Orange,Vysis)探针和CEP18(D18Z1,18p11.1-q11.1,Spectrum Aqua,Vysis)与患者的中期分裂相进行荧光原位杂交(fluorescence in situ hybridization,FISH);同时应用PCR技术对患者进行Y染色体微缺失检测。结果:结合G-显带、C-显带、FISH检测结果和Y染色体微缺失的检测结果,确定该患者核型为46,X,r(Y)(p11.3q12)[85]/45,X[15]。Yq11区生精基因微缺失检测未显示该患者存在缺失。结论:细胞遗传学检测结合FISH可以诊断复杂的染色体异常,为患者提供正确的遗传咨询和生育指导。     

Perinatal cytogenetic discrepancy in a pregnancy with mosaic 45,X/46, XY at amniocentesis and a favorable outcome

ObjectiveWe present perinatal cytogenetic discrepancy in a pregnancy with mosaic 45,X/46, XY at amniocentesis and a favorable outcome.Case reportA 38-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[2]/46,XY[6]. Level II ultrasound at 20 weeks of gestation was unremarkable, and the fetus had normal male external genitalia. Following genetic counseling, the woman decided to continue the pregnancy. At 39 weeks of gestation, a healthy male baby was delivered with a body weight of 3410 g and a body length of 54.5 cm. The male external genital organs were normal. The cord blood had a karyotype of 46, XY (40/40 cells). The umbilical cord had a karyotype of 45,X[1]/46,XY[39]. During follow-up at age one month, his body weight was 4.4 Kg (15th-50th centile), and his body length was 56 cm (50th-85th centile). The infant was doing well. Interphase fluorescence in situ hybridization analysis on 100 buccal mucosal cells revealed no abnormal Y-deletion cell, and all cells contained one Y signal.ConclusionPerinatal cytogenetic discrepancy may occur in the pregnancy with mosaic 45,X/46, XY at amniocentesis.     

Sperm ultrastructure and 18, X,Y aneuploidies in a man with a 46 XY, 47 XY + 18 mosaic karyotype: case report

Purpose To describe sperm morphology and meiotic segregation in the case of a man with a 46 XY/ 47 XY + 18 mosaic karyotype. Materials and methods A 25-year-old man came to our Centre for semen analysis. Morphological sperm evaluation was performed by light and electron microscopy; meiotic segregation was examined by fluorescence in situ hybridisation (FISH) technique using probes for chromosomes 18, X and Y. PCR was carried out on DNA from peripheral blood lymphocytes to analyze Y microdeletions. Results Mathematically elaborated transmission electron microscopy data highlighted a low number of sperm devoid of ultrastructural defects, and the presence of characteristics of apoptosis and immaturity. FISH showed the presence of aneuploidies of chromosome 18 and sex chromosomes. Conclusions In this case of mosaicism morphological and meiotic spermatogenetic impairment is shown, as well as structural chromosomal alterations. We describe sperm morphology and meiotic segregation in a carrier of 46 XY/ 47 XY + 18 mosaic karyotype.     

High incidence of Y-chromosome microdeletions in gonadal tissues from patients with 45,X/46,XY gonadal dysgenesis

A higher incidence of Y-chromosome microdeletions was found on gonadal DNA than on peripheral blood lymphocyte DNA and on streak gonads than on dysgenetic testis in 11 patients with 45,X/46,XY gonadal dysgenesis. It is probable that an association between Y-chromosome microdeletions and severity of the phenotype in 45,X/46,XY patients exists.     

Prenatal diagnosis of 45,X and 45,X mosaicism: the need for thorough cytogenetic and clinical evaluations

OBJECTIVES: Mosaicism involving a 45,X cell line is relatively common in prenatal diagnosis. In prenatally diagnosed cases, the prognosis of non-mosaic 45,X and 45,X/46,XY mosaicism are different. Therefore, accurate identification of a cell line containing Y chromosome is critical for genetic counseling and postnatal management. METHODS: We investigated the ultrasound findings and outcomes of pregnancies with a 45,X cell line identified during mid-trimester cytogenetic analysis. RESULTS: A total of 105 cases were found to have a 45,X cell line by standard cytogenetic analysis. Seventy-four cases were found to have non-mosaic 45,X at initial diagnosis. Of these 74 cases, 68 had abnormal ultrasound findings that were characteristic of Turner syndrome. Of the six cases with normal ultrasound findings, ultrasound examination was normal with male genitalia identified in three cases. Thorough cytogenetic and fluorescent in situ hybridization (FISH) analysis identified Y chromosome material in all three cases, one with a dicentric Y;14 chromosome and the other two cases with a marker chromosome containing Sex-determining Region (SRY) material in a small portion of the cells. In contrast, in 31 cases with a mosaic 45,X karyotype, ultrasound abnormality was identified only in one case. CONCLUSIONS: The present data suggest the need for follow-up ultrasound examination and thorough cytogenetic and molecular analysis for Y chromosome material in 45,X cases with normal ultrasound findings.     

45,X/46,X,del(Yq) sex chromosome mosaicism--analysis of the phenotypic expression

Three female patients with Turner-syndrome (sexual infantilism, short stature and somatic Turner-stigmata) have been analysed cytogenetically by means of different banding techniques. A deletion of the distal heterochromatic band Yq12 of the Y chromosome was observed in a mosaic with a 45,X-cell line, i.e. the karyotype is 45,X/46,X,del(Y)(q12). In order to get information about the phenotypic expression of the 45,X/46,X,del(Yq) mosaicism all previously published cases have been reviewed. Comparing the phenotypes of all 45,X/46,X,del(Yq) mosaic cases three different phenotype categories of sexual development can be distinguished: female individuals with sexual infantilism and Turner-stigmata, individuals with ambiguous genitals, ranging from clitoris hypertrophy of female genitals to hypospadia of males, male individuals, who are infertile (azoospermic). A comparison of the appearance of external genitals with the status of gonads of all patients revealed an unequivocal relationship between the gonad status and the resulting phenotype category. Furthermore, the role of Y-chromosomal loci determining testicular differentiation (biological function of H-Y antigen) for male development has been emphasized. The effect of the 45,X-cell line on the expression of short stature and somatic Turner-stigmata is independent of sexual development. Considering the great phenotypic variability of the 45,X/46,X,del(Yq) mosaicism it seems impossible to deduce a definitive phenotype. This problem is acute in prenatal diagnosis especially.     

Prenatal diagnosis of 45,X/46,XY mosaicism in a fetus with asymmetric gonadal dysgenesis

An 18 week abortus had been prenatally diagnosed as a 45,X/46,XY mosaic. The fetus was a phenotypic male with glandular hypospadias, a horseshoe kidney and asymmetric gonadal dysgenesis. This case represents a rare instance of prenatally diagnosed 45,X/46,XY mosaicism with an abnormal phenotype.     

Deoxyribonucleic acid analysis of the zinc finger Y gene in 45,X/46,XY subjects

The deoxyribonucleic acid from nine subjects with a 45,X/46,XY karyotype with a cytogenetically intact Y chromosome and phenotypically presenting with bilateral streak gonads, streak and testis, or bilateral scrotal testes along with a control male and female were analyzed for the presence of the zinc finger Y sequence through the molecular probe pDP1007. This particular probe is thought to constitute part of the putative testicular-determining factor gene. All the study subjects demonstrated the presence of zinc finger Y. Laser densitometry studies confirmed a correlation between the intensity of the zinc finger Y band and the percentage of Y cell lines. This study supports the fact that individuals with mixed gonadal dysgenesis and cytogenetically intact Y chromosomes will tend to have intact zinc finger Y sequences.     

Analysis of Spermatozoa from Seven ICSI Males with Constitutional Sex Chromosomal Abnormalities by Fluorescent In Situ Hybridization

Purpose: The objective was to estimate the risk for subfertilemales with a constitutional sex chromosomal abnormalityof transmitting such a chromosome abnormality to theirchildren, conceived by intracytoplasmic sperm injection(ICSI). Methods: Semen samples were obtained from seven severelyoligospermic ICSI candidates. Six of them had a numericalsex chromosomal abnormality, including mosaic 45,X/46,XY,mosaic 46,XY/47, XXY, 47,XXY (Klinefelter's syndrome), and47,XYY. One male had a structural abnormality, namely, aninversion of the Y chromosome. The semen was studied bythree-color fluorescent in situ hybridization (FISH) withprobes specific for chromosomes 18,X, and Y. Results: Chromosomal aneuploidy rates of any of the threechromosomes were significantly higher than the aneuploidyrates observed in three control samples but comparable tothe rates observed in 10 ICSI candidates witholigoasthenoteratozoospermia (OAT) and a normal constitutionalkaryotype. Conclusions: Our data indicate that males with (mosaic) sexchromosomal abnormalities have no higher risk of producingoffspring with a sex chromosomal abnormality by ICSI thanOAT males with a normal karyotype.     

516例无精症Y染色体微缺失及细胞遗传学分析

目的 探讨Y染色体微缺失和细胞遗传学分析在无精症中的相关性.方法 对2015年3月至2019年12月来广东省妇幼保健院就诊的诊断为无精症的患者进行外周血染色体G显带核型分析,运用多重定量荧光聚合酶链反应(quantitative fluorescent PCR,QF-PCR)技术检测Y染色体上的无精因子(azoospe...     

Turner综合征患者标记染色体的鉴定与分析

目的 分析11例携带标记染色体的Turner综合征患者的核型,研究这类染色体的表型效应。方法 选择11例具Turner综合征表型的患者,常规核型分析均显示为携带标记染色体的嵌合体,其中6例标记染色体呈环状。患者G带核型表示为mos．45,X／46,X,＋mar或者mos．45,X／46,X,＋r．以X／Y着丝粒探针,应用荧光原位杂交（FISH）技术分析这些标记染色体起源,对其中2例较大的环状染色体,结合反向染色体涂染确定断裂位点,比较不同断裂位点的标记染色体的遗传学效应。结果11例患者所携带的标记染色体均为环状染色体,r（X）的断裂位点分别位于Xp22、Xq22、Xq24、Xq26等。结论 Turner综合征患者的标记染色体主要来源于X染色体,且表现为r（X）形式。r（X）均以嵌合型的形式存在。     

Hormonal and cytogenetic studies in phenotypically female patients with gonadal dysgenesis

In 4 cases of gonadal dysgenesis the clinical, hormonal, cytogenetic, and histological findings were correlated. There were 2 patients with 46,XY karyotype, one patient with 45,X Turner's syndrome and one patient with a 46,XX chromosome complement. All patients had streak gonads with ovarian stroma. In one phenotypically female 46,XY individual an involuted gonadoblastoma was found. Her testosterone was four-fold higher in gonadal vein blood compared to peripheral blood. Cytogenetic analysis of multiple tissues in both cases with the 46,XY karyotype greatly reduced the probability of mosaicism. In the patient with 45,X Turner's syndrome and in the one with 46,XX gonadal dysgenesis only peripheral blood cells were karyotyped and mosaicism was not further excluded by analysis of other tissues. The concentrations of steroid hormones in gonadal vein blood were low. The levels ranged as follows: estrone 41-98 pg/ml, estradiol 18-90 pg/ml, testosterone 37-294 ng/100 ml, dihydrotestosterone 13-22 ng/100 ml, and progesterone 0.3-1.5 ng/ml. It was concluded that gonadal streaks were similarly deficient in biosynthesis of steroid hormones despite different chromosomal complements.     

Prenatal and postnatal characterization of Y chromosome structural anomalies by molecular cytogenetic analysis

We describe three cases in which we used fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) and comparative genomic hybridization (CGH) to characterize Y chromosome structural anomalies, unidentifiable by conventional G-banding. Case 1 was a 46,X,+mar karyotype; FISH analysis revealed an entire marker chromosome highlighted after hybridization with the Y chromosome painting probe. The PCR study showed the presence of Y chromosome markers AMG and SY620 and the absence of SY143, SY254 and SY147. CGH results confirmed the loss of Yq11.2-qter. These results indicated the presence of a deletion: del(Y)(q11.2). Case 2 was a 45,X [14]/46,XY[86] karyotype with a very small Y chromosome. The PCR study showed the presence of Y chromosome markers SY620 and AMG, and the absence of SY143, SY254 and SY147. CGH results showed gain of Yq11.2-pter and loss of Yq11.2-q12. These results show the presence of a Yp isodicentric: idic(Y)(q11.2). Case 3 was a 45,X,inv(9)(p11q12)[30]/46,X,idic(Y)(p11.3?),inv(9)(p11q12)[70] karyotype. The FISH signal covered all the abnormal Y chromosome using a Y chromosome paint. The PCR study showed the presence of Y chromosome markers AMG, SY620, SY143, SY254 and SY147. CGH only showed gain of Yq11.2-qter. These results support the presence of an unbalanced (Y;Y) translocation. Our results show that the combined use of molecular and classical cytogenetic methods in clinical diagnosis may allow a better delineation of the chromosome regions implicated in specific clinical disorders.     

Bilateral seminomas in a 45X/46XY mosaic with Turner's phenotype: an unusual case of mixed gonadal dysgenesis

A wide spectrum of phenotypic manifestations are seen in cases with 45X/46XY mosaicism. We present a case with 45X/46XY having female phenotype with Turner's stigmata. Prophylactic laparoscopic gonadectomy was performed and the patient was found to have mixed gonadal dysgenesis with bilateral gonadoblastomas. Microinvasive seminomas were also detected in both gonadoblastomas. The presence of Y cell line in karyotype prompted early and prophylactic gonadectomy, a procedure which is life-saving for these individuals.