X-autosome translocations in amenorrhoea: a report of a three way translocation from Indian Population

Chromosomal translocations have been reported in a number of women undergoing cytogenetic studies for amenorrhoea and gonadal dysgenesis. This study was taken up to emphasize the role of X chromosome and to know the frequency of X-autosomal translocations in women with amenorrhoea in Indian population. Cytogenetic analysis was carried out in 1567 subjects referred for amenorrhoea during the period 2002–2012. GTG-banding was performed from peripheral blood lymphocyte cultures to detect the chromosome abnormalities in all the cases. The karyotype results revealed 43.6% cases with chromosomal abnormalities (n?=?683 of 1567 cases). The X-autosomal translocations was found in 2.64% (n?=?18 of 683 cases). The common chromosomes involved with X were chromosomes 2, 4, 14 and 20. The translocations involved both p and q arms of the X chromosome.The break point “q26” of X was observed in the majority of the cases. Two interesting cases are discussed: one with three way translocation and another with two translocations. A high number of primary amenorrhoea (PA) and secondary amenorrhoea (SA) cases were involved in X-auto translocation which clearly reveals that chromosomal analysis plays an important role in the evaluation of amenorrhoea.     

月经紊乱患者的细胞遗传学分析

目的 分析原发闭经、继发闭经及月经稀发患者的染色体核型,探讨性染色体异常对性腺发育的影响。方法 将176例患者分为两组,其中82例原发闭经组,94例继发闭经及月经稀发组。每例行外周血培养,制片及G显带,并行染色体核型分析。结果 176例患者发现性染色体异常38例,异常检出率为29.6％(38/176),其中原发闭经组33例,异常检出率为40.2％(33/82);继发闭经及月经稀发组检出性染色体异常5例,异常检出率为5.3％(5/94);两组异常检出率差异有显著性(P<0.05)。性染色体异常大体上分为三大类:含Y染色体(15例),X染色体数目异常(18例),X染色体结构异常(5例),嵌合体均以45,X系为主,共10例。结论 两条完整的染色体是女性性腺发育及正常卵巢功能所必须,性染色体异常是原发闭经的主要原因之一,常规细胞遗传学检查是必要的;继发闭经及月经稀发也不应忽视此项检查。     

Cytogenetic analysis of 179 Iranian women with premature ovarian failure

Abstract

The importance of chromosomal abnormalities in etiology of premature ovarian failure (POF) is well known but in many cases, POF still remains idiopathic. We investigated the frequency and type of chromosomal aberrations in Iranian women diagnosed with idiopathic POF. Standard cytogenetic analysis was carried out in a total of 179 patients. Karyotype analysis of these patients revealed that 161 (89.95%) patients had normal female karyotype and 18 (10.05%) patients had abnormal karyotypes. The abnormal karyotypes included sex reverse sex determining region Y (SRY) negative (five Cases), X chromosome mosaicism (five cases), abnormal X chromosomes (three cases), abnormal autosomes (three cases) and X-autosome translocation (two cases). The overall prevalence of chromosomal abnormalities was 10.05% in this first large-scale report of chromosomal aberrations in Iranian women with POF. The results confirm previous observations and emphasis on the critical role of X chromosome abnormalities as one of the possible etiologies for POF.     

Secondary amenorrhoea: prevalence and medical contact--a cross-sectional study from a Danish county.

OBJECTIVE: To examine the prevalence of secondary amenorrhoea and the patterns of seeking medical advice for secondary amenorrhoea in an unselected population. DESIGN: Cross-sectional postal questionnaire study. SETTING: County of Copenhagen, Denmark. SUBJECTS: 3743 women, aged 15-44, selected at random from a Danish county who were asked to provide information on menstrual patterns for the preceding year, 1988. The response rate was 78%. Information from non-responders was obtained via telephone interviews. RESULTS: One-year period prevalence of secondary amenorrhoea of more than 3 months duration was 4.6% and was 7.6%, 3.0%, and 3.7% in women aged 15-24, 25-34, and 35-44 respectively. The duration of secondary amenorrhoea was 6 months or less in 75% aged 15-34 years, but longer than 6 months in 55% of those aged 35-44 years. A social gradient was found of the prevalence of secondary amenorrhoea (odds ratio 3.3, 95% CI 1.5-8.3) in the lowest social group compared with the highest social group; controlled by age. Only 39% of women with secondary amenorrhoea had contacted a doctor. Educational level or social status did not seem to influence the frequency of medical contact in women with amenorrhoea. CONCLUSION: Spontaneous return of the menstrual cycle occurs within 6 months in many amenorrheic women below the age of 35. The detailed investigation of secondary amenorrhoea in this age group can be postponed until it is of 6 months duration, unless there is clinical suspicion of disease. The relative infrequency with which women with secondary amenorrhoea seek medical advice constitutes an important source of selection bias in hospital-based clinical research on this topic.     

Infrequent structural chromosome aberrations in women with primary amenorrhea.

Since the problem of primary amenorrhoea (PA) is very real the authors reviewed a series of 58 women from their own laboratory, citing all known causes of PA and emphasizing that the most interesting cases are those with normal karyotype. Reinvestigation of patients with normal karyotype using the banding methods (G and R) revealed new types of structural aberrations of X chromosome. The importance of structural disturbances and rearrangements of particular segments of X chromosome in the etiology of PA has been discussed.     

Recurrent pregnancy losses and parental chromosome abnormalities: a review

Summary. A compilation of the cytogenetic results taken from 79 published surveys of couples with two or more pregnancy losses (comprising 8208 women and 7834 men) showed an overall prevalence of major chromosome abnormalities of 2.9%. This is five to six times higher than that of the general adult population. In every group of chromosome abnormalities in the parents a predominance of female to male affected was noted (2:1). Approximately 50% of all chromosome abnormalities detected were balanced reciprocal translocations, 24% were Robertsonian translocations, 12% were sex chromosomal mosaicisms in females, and the rest consisted of inversions and other sporadic abnormalities. Parents with two or more idiopathic pregnancy losses should be karyotyped to aid in management and counselling. When a translocation or other abnormality (e.g. X chromosomal mosaicism) predisposing to an abnormal zygote is found, prenatal diagnosis is indicated in future pregnancies. Even when parental karyotypes are normal, prenatal diagnosis should be considered in subsequent pregnancies of parents with two or more pregnancy losses because of the high incidence of chromosome abnormalities in spontaneous abortions. For the same reason, if a single previous pregnancy loss is known to have been chromosomally aneuploid, parental karyotypes may have to be examined (depending upon the finding in the pregnancy loss), and prenatal diagnosis should also be considered in subsequent pregnancies.     

Recurrent pregnancy losses and parental chromosome abnormalities: a review

A compilation of the cytogenetic results taken from 79 published surveys of couples with two or more pregnancy losses (comprising 8208 women and 7834 men) showed an overall prevalence of major chromosome abnormalities of 2.9%. This is five to six times higher than that of the general adult population. In every group of chromosome abnormalities in the parents a predominance of female to male affected was noted (2:1). Approximately 50% of all chromosome abnormalities detected were balanced reciprocal translocations, 24% were Robertsonian translocations, 12% were sex chromosomal mosaicisms in females, and the rest consisted of inversions and other sporadic abnormalities. Parents with two or more idiopathic pregnancy losses should be karyotyped to aid in management and counselling. When a translocation or other abnormality (e.g. X chromosomal mosaicism) predisposing to an abnormal zygote is found, prenatal diagnosis is indicated in future pregnancies. Even when parental karyotypes are normal, prenatal diagnosis should be considered in subsequent pregnancies of parents with two or more pregnancy losses because of the high incidence of chromosome abnormalities in spontaneous abortions. For the same reason, if a single previous pregnancy loss is known to have been chromosomally aneuploid, parental karyotypes may have to be examined (depending upon the finding in the pregnancy loss), and prenatal diagnosis should also be considered in subsequent pregnancies.     

Malignant Stromal Tumour of the Ovary with Virilizing Effects in an XXX Female with Streak Ovaries

Summary: In gonadal dysgenesis, the presence of the Y sex chromosome appears to have a strong influence on the development of germ cell tumours. The risk of malignancy associated with other sex chromosomal abnormalities is much lower. In the present report, the clinical manifestations – including primary amenorrhoea, tall stature, infertility and poor development of the genitalia and breasts – associated with a predominantly 47, XXX karyotype are described. Malignant change of the streak ovary to an unusual gonadal stromal tumour with lipid-containing cells occurred at a late stage in her life, and this was associated with progressive virilization and production of androgenic and oestrogenic steroids. In view of the risk of malignancy as well as the abnormal endocrine effects, especially in the presence of a Y chromosome, there is a place for the prophylactic removal of these dysgenetic gonads.     

ACOG Practice Bulletin No. 88, December 2007. Invasive prenatal testing for aneuploidy

Prenatal diagnosis of fetal chromosomal abnormalities is the most common indication for invasive prenatal testing. The prevalence of chromosomal abnormalities in clinically recognized early pregnancy loss is greater than 50%(1). Fetuses with aneuploidy account for 6-11% of all still births and neonatal deaths(2). Chromosomal abnormalities that are compatible with life but cause considerable morbidity occur in 0.65% of newborns, and structural chromosomal rearrangements that will eventually affect reproduction occur in 0.2% of newborns(3). Consequently, screening and diagnostic programs to detect the most common autosomal trisomies in liveborn infants, including Down syndrome, are well established. The purpose of this document is to provide clinical management guidelines for the prenatal diagnosis of these aneuploidies.     

Y chromosome mosaicism and occurrence of gonadoblastoma in cases of Turner syndrome and amenorrhoea

In the present study, 73 cases with a clinical diagnosis of Turner syndrome, or with primary or secondary amenorrhoea without frank Turner phenotype, were evaluated for presence of low level Y chromosome mosaicism using molecular methods. Fluorescence in-situ hybridization for centromere and q arm of the Y chromosome and nested polymerase chain reaction for the sex determining region on Y (SRY) gene were performed in peripheral blood, buccal cells and gonadal biopsies. The overall frequency of Y chromosome mosaicism was found to be 18% (13/73 cases). Four cases (16%) of Turner syndrome had Y chromosome mosaicism, seven cases (28%) with primary amenorrhoea and two cases (9%) with secondary amenorrhoea had Y chromosome mosaicism. Histologically detectable gonadoblastoma was observed in one of seven cases (14%) that had Y chromosome mosaicism. This frequency is lower than that reported previously, underscoring the need for large prospective investigations to determine the frequency of Y chromosome mosaicism and occurrence of gonadoblastoma in cases of Turner syndrome and other forms of amenorrhoea.     

First trimester sonographic detection of chromosomal abnormalities in an unselected population

Objective To investigate the role of first trimester sonography in detecting chromosomal abnormalities in an unselected obstetric population.
Methods 2281 women (mean maternal age 30 years [range 16-47]; mean gestational age 12⁺³ weeks [range 11-14]) underwent transabdominal scanning to assess fetal structure and, if anatomical survey was considered to be incomplete (31% of cases), transvaginal sonography was also performed. Measurement of nuchal translucency was included and karyotyping performed as considered appropriate.
Results There were 16 chromosomal abnormalities; 13 (81%) were diagnosed at 11-14 weeks either because of a nuchal translucency greater than or equal to the 99th centile for gestational age (7/16; 44% [95% CI 25-63]) or due to the presence of structural abnormalities (6/16; 38% [95%CI 14.2–61.81). Seventy-five percent of cases of trisomy 21 were also diagnosed either because of having a nuchal translucency greater than or equal to the 99th centile (5/8; 63%) or due to the presence of a structural abnormality (1/8; 13%).
Conclusions A significant proportion of fetal chromosomal abnormalities can be detected by first trimester sonographic screening to assess fetal structural appearance. The sensitivity of detection can be improved by combining measurement of nuchal translucency with detailed examination of fetal anatomy.     

The value of sonography in early pregnancy for the detection of fetal abnormalities in an unselected population.

OBJECTIVE: To determine the value of early pregnancy sonography in detecting fetal abnormalities in an unselected obstetric population. DESIGN Prospective cross-sectional study. All women initially underwent transabdominal sonography and when the anatomical survey was considered to be incomplete, transvaginal sonography was also performed (20.1%). Nuchal translucency was measured and karyotyping was performed as appropriate. SETTING: University Department of Obstetrics and Gynaecology. PARTICIPANTS: 6634 sequential unselected women (mean maternal age 29.9 years, range 13-50; mean gestational age 12+4 weeks, range 11+0-14+6), carrying 6443 live fetuses participated in this study. MAIN OUTCOME MEASURE: Detection rate of fetal anomalies and the associated cost per case detected in early pregnancy. RESULTS: The incidence of anomalous fetuses was 1.4% (92/6443) including 43 chromosomal abnormalities. The detection rate for structural abnormalities was 59.0% (37/63, 95% CI 46.5-72.4) and the specificity was 99.9% in early pregnancy. When the first and second trimester scans were combined, the detection for structural abnormalities was 81.0% (51/63, 95% CI 67.7-89.2). Seventy-eight percent (31/40) of chromosomal abnormalities (excluding three cases of XXY) were diagnosed at 11-14 weeks, either because of a nuchal translucency greater than or equal to the 99th centile for gestational age (43%; 17/40, 95% CI 27.4-60.4), or due to the presence of structural abnormalities (35%; 14/40, 95% CI 21.2-52.8). Sixty-five percent (15/23) of cases of trisomy 21 were also diagnosed either because of having a nuchal translucency greater than or equal to the 99th centile (57.0%; 13/23) or due to the presence of a structural abnormality (9.0%; 2/23). Overall, the detection rate of structurally abnormal fetuses was 59% (37/63) in early pregnancy and 81% in combination with the second trimester scan. The cost per abnormality diagnosed in early pregnancy is estimated to be pound sterling 6258 per structurally abnormal fetus, pound sterling 7470 per chromosomal abnormality and pound sterling 4453 per anomalous fetus. CONCLUSION: The majority of fetal structural and chromosomal abnormalities can be detected by sonographic screening at 11-14 weeks, but the second trimester scan should not be abandoned.     

Primary Amenorrhoea in a Triple X Female

The incidence of trisomy X in the newborn population is estimated to be 1 in 1,000 liveborn females. Most of them have normal physical appearance and puberty. Therefore, the reported number of triple X females in the literature is low. We herein report one patient with triple X chromosomes, primary amenorrhoea and normal intelligence. Steroid hormonal levels, clinical and ultrasound findings were suggestive of ovarian failure/gonadal dysgenesis. This case emphasizes the need for chromosomal analysis in women presenting with premature ovarian failure leading to primary or secondary amenorrhoea.     

Chromosomal abnormalities associated with neural tube defects (I): full aneuploidy

Fetuses with neural tube defects (NTDs) carry a risk of chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with other structural abnormalities, and family history of chromosome aberrations. This article provides an overview of chromosomal abnormalities associated with NTDs in embryos, fetuses, and newborn patients, and a comprehensive review of numerical chromosomal abnormalities associated with NTDs, such as trisomy 18, trisomy 13, triploidy, trisomy 9, trisomy 2, trisomy 21, trisomy 7, trisomy 8, trisomy 14, trisomy 15, trisomy 16, trisomy 5 mosaicism, trisomy 11 mosaicism, trisomy 20 mosaicism, monosomy X, and tetraploidy. NTDs may be associated with aneuploidy. Perinatal identification of NTDs should alert one to the possibility of chromosomal abnormalities and prompt a thorough cytogenetic investigation and genetic counseling.     

Evaluation of sex chromosome aneuploidies in women with Turner's syndrome by G-banding and FISH. A serial case study

OBJECTIVE: To evaluate sex chromosome aneuploidies in patients with Turner's syndrome using two cytogenetic techniques. STUDY DESIGN: A sample of 35 women with a clinical suspicion of Turner syndrome was examined in the Hospital of Obstetrics and Gynecology, Instituto Mexicano del Seguro Social, Monterrey, Mexico. They were subjected to a conventional cytogenetic technique with G-banding and to fluorescence in situ hybridization (FISH) using a specific alpha satellite X chromosome (DXZ1) and specific alpha satellite Y chromosome (DYZ1). RESULTS: Using both techniques, 17 cases (48.57%) showed the same karyotype. Using FISH: (1) in 8 cases the presence of the Y chromosome was confirmed, (2) in 18 cases (51.43%) a new cell line was identified, (3) in 2 cases (5.71%) the derivative X was clarified, and (4) in 3 cases (8.57%) the origin of the chromosome markers (1 of X chromosome and 2 of Y chromosome) was delineated. FISH highlighted the differences between the initial diagnosis, based on G-banding, and the final diagnosis, determined by specific probes for the X and Y chromosomes. CONCLUSION: FISH is a useful tool in the detection of low-frequency cell lines and identification of the nature and origin of derivative chromosomes and unknown chromosome markers that have important implications for the treatment of patients with Turner's syndrome.     

Chromosome abnormalities detected in chorionic villus biopsies of failing pregnancies in a subfertile population.

OBJECTIVE--To determine the range and prevalence of chromosomal abnormalities occurring in failing pregnancies in subfertile women. DESIGN--Prospective biochemical and ultrasound monitoring of all pregnancies conceived between 1988 and 1990 in a subfertile population. SETTING--A single-centre specialist fertility clinic in Perth, Western Australia. SUBJECTS--Tissue from 50 early pregnancy losses was successfully cultured for chromosomal analysis from 46 pregnancies comprising 29 anembryonic pregnancies, 9 miscarriages and 8 ectopic pregnancies. MAIN OUTCOME MEASURES--Impending pregnancy loss was identified at an early stage. Chromosomal analysis was performed on chorionic villi obtained before the diagnosis became clinically evident. RESULTS--Significant chromosomal abnormalities were identified in 54% (14/26) of early pregnancy losses where gamete manipulation was involved and 45% (9/20) of those following spontaneous conception. The most common abnormalities were trisomies (12 pregnancies, mainly trisomy 16), triploidies (3 pregnancies) and monosomy X (3 pregnancies). An excess of female fetuses was noted with only 24% of conceptuses (11/46) bearing a Y chromosome. CONCLUSIONS--The data indicate a similar rate of chromosomal abnormalities underlying pregnancy losses at earlier stages of pregnancy and after infertility treatments as that reported from the general population. Gamete manipulation does not appear to confer a higher rate of chromosomal abnormalities in ensuing pregnancies.     

Chromosomal anomalies in first-trimester miscarriages

BACKGROUND. It is well known that a large proportion of first-trimester spontaneous abortions is caused by chromosomal disorders. The present study represents a unique material and the success rate of the karyotyping was high. METHODS. Chromosomal analysis from chorionic villus sampling of 259 of 304 consecutive first-trimester miscarriages in the Uppsala County, Sweden is presented. RESULTS AND CONCLUSIONS. An abnormal karyotype was found in 61% of the cases. Autosomal trisomies were most frequently detected (in 37% of the karyotyped samples), followed by polyploidies (9%) and monosomy X (6%). Cases with an extra sex chromosome constituted approximately 5% of the karyotyped abortions, with a remarkable high frequency of 47,XXY (3.4%), that is approximately 40 times greater the prevalence of Klinefelter syndrome among live birth. Similar to autosomal chromosome abnormalities, present finding indicates that the majority of sex chromosome abnormalities do not survive to term. Autosomal trisomies and an extra X-chromosome in males (47,XXY) were associated with an advanced maternal age, whereas monosomy X as well as polyploidy changes seems to be inversely related to the age of the mother. The single most common aberration was trisomy 16, which was found in 14% of the chromosomally abnormal abortions.     

Gonadal dysgenesis in own material]

Eleven patients with Turner syndrome and 6 with pure gonadal dysgenesis were examined. Diagnosis was made on the base of clinical and cytogenetic examination. All patients had primary amenorrhea and underdevelopment of primary, secondary and tertiary sexual features. Hormonal estimations revealed elevated FSH serum concentration in women with Turner syndrome and with pure gonadal dysgenesis (46, XY) vs. to patients with 46, XX. Estradiol and Progesterone levels were low in all cases. All women were treated with estrogens and progestational agents in sequential manner with good results. We did not observe significant phenotypic differences between patients with monosomie X and patients with structural abnormalities within chromosome X and mosaicism.     

胎儿颈项透明层增厚和静脉导管血流频谱异常与胎儿染色体异常的关系

目的探讨胎儿颈项透明层(nuchal translucency, NT)超声检查在早孕期胎儿筛查中的应用价值。 方法收集104例于广州市妇女儿童医疗中心诊断NT增厚的孕妇的染色体核型分析资料,回顾性分析胎儿NT增厚、静脉导管血流频谱异常与胎儿染色体异常的关系。 结果(1)9980例孕妇中,NT异常增厚的胎儿共104例,占1.0%,颈项透明层厚度为(3.7±1.2)mm;(2)104例NT异常增厚的胎儿中,有28例胎儿染色体核型异常,包括染色体数目异常22例,结构异常6例,其中前3位为21-三体综合征、18-三体综合征和47,XXX;(3)随着NT厚度的增加,染色体异常的检出率相应增加;(4)NT增厚及静脉导管血流频谱正常预测染色体异常的阳性预测值是20.93%,NT增厚及静脉导管血流频谱异常的阳性预测值是55.56%,其差异具有统计学意义( χ²＝7.07,P<0.01)。 结论在早孕期进行胎儿NT超声检查,NT增厚及静脉导管血流频谱异常联合筛查更能有效筛查出染色体核型异常的高危胎儿。     

1981例高龄孕妇的产前细胞遗传学诊断

目的通过高龄孕妇产前胎儿染色体核型结果分析,探讨高龄妊娠胎儿染色体异常的风险。方法通过对高龄孕妇羊水穿刺1807例和脐带血穿刺174例染色体核型分析,探讨高龄妊娠胎儿染色体异常的比率,对比35～37岁、38～40岁、≥41岁三组孕妇胎儿染色体异常发生率,分析不同高龄组胎儿染色体异常的风险比率。结果 1981例高龄孕妇共发现胎儿染色体核型异常61例,染色体异常发生率为3.08%,且随孕妇年龄增长,胎儿染色体异常的发生率显著增高(P0.01)。结论随着孕妇年龄增长,胎儿染色体异常风险逐渐增高,高龄孕妇有必要行产前诊断。