Prenatal diagnosis of mos46,X,del(Y)(q11.2)/45,X by cytogenetic and molecular studies with multiplex STR analysis

OBJECTIVES: To present the prenatal diagnosis of a fetus of mos46,X,del(Y)(q11.2)/45,X by cytogenetic and molecular analysis. CASE AND METHODS: A 35-year-old pregnant woman came to our hospital for amniocentesis, and fetal chromosomal aberrations with mos46,X, + mar/45,X were found. Fluorescence in situ hybridization revealed the existence of a Y centromere on the marker chromosome. Analysis with six pairs of short tandem repeat markers showed that the genomic DNA extracted from the uncultured amniotic fluid cells contained a deletion of Yq11.1-Yq11.2. Spermatogenesis loci of the Y chromosome were studied using four sets of multiplex PCR. The proximal two markers DYS271 and KALY were present and the other 16 distal markers were deleted. No deletion was noted in the Y chromosome of the father. RESULTS: Cytogenetic and molecular analyses revealed deletions of AZFb, d, and c regions on Yq11.2-Yqter in the fetal Y chromosome. Postmortem examination of the fetus showed a grossly normal male fetus with normal external genitalia and testes. CONCLUSION: The present report demonstrates that molecular analysis using polymorphic microsatellite markers and multiplex PCR is a useful complement to cytogenetic methods for the identification and the characterization of Y-chromosomal deletions.     

Meiotic behavior of the sex chromosomes in a 45,X/46,X,r(Y)/46,X,dic r(Y) patient whose semen was assessed by fluorescence in situ hybridization

OBJECTIVE: To determine the meiotic behavior of a ring Y chromosome in a semen sample from a 45,X/46,X,r(Y)/46,X,dic r(Y) patient and the possible interchromosomal effects of the ring on other chromosome pairs. DESIGN: Retrospective analysis. SETTING: Universitat Autònoma de Barcelona. PATIENT: An oligoasthenoteratozoospermic patient who presented for infertility consultation. MAIN OUTCOME MEASURE(S): The sex chromosome content of spermatogenic cells, meiotic figures, and spermatozoa in the ejaculate and the possible interchromosomal effects on chromosomes 13, 18, and 21 were analyzed by using multicolor fluorescence in situ hybridization. Germ-cell aneuploidies were scored. RESULT(S): X0 cells are meiotically incompetent. All meiotic figures were exclusively XY, and 80% showed unpaired sex chromosomes. A high proportion of postreductional cells were XY (45.5%) or nullisomic for sex chromosomes (13.92%). This percentage decreased in spermatozoa to 14.89% and 27.66%, respectively. A statistically significant increase in X-bearing versus Y-bearing cells both in postreductional cells (23.9% vs. 14.3%) and spermatozoa (41.9% vs. 19.3%) was also observed. Evidence for an interchromosomal effect on chromosome 21 was detected. CONCLUSION(S): Data suggest that this patient had a generalized increase incidence of chromosome anomalies, underscoring the importance of incorporating screening for sperm aneuploidies in genetic analysis of affected patients.     

High-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis in a pregnancy with a favorable outcome and postnatal progressive decrease of the 45,X cell line

ObjectiveWe present prenatal diagnosis of high-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis in a pregnancy with a favorable outcome and postnatal progressive decrease of the 45,X cell line.Case reportA 36-year-old, gravida 4, para 3, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[22]/46,X,idic(Y)(q11.2)[4]. Prenatal ultrasound was unremarkable, and the fetus had normal male external genitalia. Repeat amniocentesis was performed at 20 weeks of gestation, and the second amniocentesis revealed a karyotype of 45,X[24]/46,X,idic(Y)(q11.2)[3]. Simultaneous interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed that 60% (62/103 cells) were Y-deleted cells. After genetic counseling, the parents decided to continue the pregnancy, and a 3020-g male baby was delivered with a body length of 52 cm, normal male genital organs and no phenotypic abnormalities. The karyotypes of cord blood, umbilical cord and placenta were 45,X[20]/46,X,idic(Y)(q11.2)[20], 45,X[31]/46,X,idic(Y)(q11.2)[9] and 45,X[40], respectively. At age one month, FISH analysis on urinary cells and buccal mucosal cells revealed 11.5% (7/61 cells) and 13.6% (16/118 cells), respectively for mosaicism for the Y-deleted cells. At age five month, the karyotype of peripheral blood was 45,X[9]/46,X,idic(Y)(q11.2)[31]. FISH analysis on buccal mucosal cells showed no abnormal Y-deleted cell (0/101 cells). At age 11 month, the karyotype of peripheral blood was 45,X[5]/46,X,idic(Y)(q11.2)[35]. FISH analysis on 102 buccal mucosal cells showed no abnormal signals. The infant was doing well with normal physical and psychomotor development.ConclusionHigh-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis can be associated with a favorable outcome and progressive decrease of the 45,X cell line.     

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.     

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。     

Sonographic genital ambiguity in a fetus due to a mosaic 45,X/46,X,idic(Y)(qter-p11.32::p11.32-qter) karyotype

Nowadays, improved ultrasound techniques enable the detection of more subtle congenital abnormalities at an earlier stage of fetal development. Current cytogenetic techniques can characterize a chromosomal abnormality in greater detail. These advancements in both diagnostic possibilities have helped to answer many questions but have also created new issues and dilemmas in counselling. This is illustrated by this case report of a 35-year-old woman, who presented at the end of the second trimester of her first pregnancy. Sonographic examination indicated an abnormal external genital in a male fetus. A differential diagnosis of hypospadia was made. During follow-up, an amniocentesis was performed, and this showed a 45,X/46,X,idic(Y)(qter-p11.32::p11.32-qter) karyotype as the cause of the sonographic findings. Cytogenetic characterization of the isodicentric Y chromosome and pre- and post-natal findings in the child are reported. Cases with a similar karyotype reported in the literature are reviewed.     

Advanced FISH with directly labeled X, Y and 18 DNA probes as a tool for rapid prenatal diagnosis.

OBJECTIVE: To examine a rapid technique for identification and determination of fetal sex chromosomes and one autosome (chromosome 18) in uncultured amniotic fluids using fluorescence in situ hybridization (FISH) with directly labeled DNA probes and ignoring the use of proteinase K and Rnase. STUDY DESIGN: Twenty-five amniotic samples taken from pregnant women who were in their 18th gestational week and had advanced maternal age were studied for analysis of sex chromosomes and chromosome 18 with the FISH technique as well as standard cytogenetic analysis. RESULTS: Four hours after amniocentesis was performed, we identified the sex of the fetuses and disomy of chromosome 18 in a minimal sample of uncultured amniotic fluid by using directly labeled DNA probes for chromosomes X, Y and 18 (VYSIS) and ignoring the use of proteinase K and Rnase. CONCLUSION: The possibility of shortening the time required for identification of aneuploidies in a second-trimester fetus is useful in cases where fetal anomalies are ultrasonically diagnosed at a relatively advanced gestational age.     

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.     

Discrepancy between cytogenetic and FISH results on an amniotic fluid sample of 45,X/46,X,idic(Y)(p11)

The presence of abnormal ultrasound markers showing a thick nuchal fold with short middle phalanx of the fifth finger in an otherwise normal-appearing female fetus led to the sampling of amniotic fluid at 16 weeks gestation. Cytogenetic analysis with routine G-banding showed a 45,X karyotype in all 20 cells analysed from two flasks. However, fluorescent in situ hybridization on uncultured cells showed presence of a Y signal in 9 cells, 11 cells showing a single signal for the X. A cytogenetic analysis of the fetal blood at 23 weeks confirmed the presence of two cell lines, 45,X and 46,X, idic(Y)(p11). The couple opted to have the pregnancy terminated. However, the fetus was not available to carry out confirmatory tests.     

Increased chromosome X, Y, and 18 nondisjunction in sperm from infertile patients that were identified as normal by strict morphology: implication for intracytoplasmic sperm injection.

OBJECTIVE: To determine the incidence of nondisjunction for chromosomes X, Y, and 18 using fluorescence in situ hybridization (FISH) on morphologically normal sperm from infertile men who are candidates for ICSI. DESIGN: After standard hematoxylin staining, sperm with normal morphology were identified using Kruger's strict morphology criteria. The location of each normal-appearing sperm was recorded using an electronic microstage locator. Slides were subsequently subjected to FISH for detection of chromosomes X, Y, and 18 (control probe). Nuclei were relocated and analyzed under the fluorescent microscope. SETTING: University-affiliated IVF and intracytoplasmic sperm injection program. PATIENT(s): Men classified as infertile on the basis of abnormal strict morphology (<4% by Kruger's criteria). For controls, normal fertile men (n=6) were also analyzed. INTERVENTION(S): Semen smears were obtained retrospectively from infertile (n=8) and fertile (n=6) men. MAIN OUTCOME MEASURE(s): Ploidy of each cell was determined according to the number of signals detected for each probe. RESULT(S): Approximately 100-150 morphologically normal sperm were identified and located in each case. Subsequent FISH analysis of these normal sperm showed aneuploidy to range from 1.8% to 5.5% in the infertile group as compared with 0 to 2.6% among the control fertile group. Statistically significant differences in the incidence of aneuploidy for the sex chromosomes as well as for all three (X, Y, and 18) chromosomes was observed. CONCLUSION(S): Although 95% to 98% of the sperm were found to be normal for X, Y, and 18, our findings show that infertile couples undergoing ICSI are likely to be at an increased risk for having a genetically abnormal conceptus as compared with the fertile controls. These results demonstrate that normal morphology is not an absolute indicator for the selection of genetically normal sperm. Hence, observed pregnancy failures among ICSI patients may in part be due to the selection of aneuploid sperm.     

Validation of primed in situ labeling for interphase analysis of chromosomes 18, X,and Y in uncultured amniocytes

OBJECTIVE: Primed in situ labeling (PRINS) is an interesting alternative to the traditional fluorescence in situ hybridization (FISH) for the in situ detection of specific sequences in chromosome anomalies. It combines the sensitivity and specificity of the polymerase chain reaction with the specific in situ signal detection capability of FISH. METHODS: We performed PRINS on uncultured amniocytes and compared the results with standard cytogenetic analysis. In a prospective study, a total of 262 independent samples were analyzed for numerical aberrations of chromosome 18. RESULTS: In more than 95% of the cases PRINS reactions were successfully achieved. Neither false-positive nor false-negative results were obtained. 62 of the 262 cases were in parallel examined for chromosome 18 aneuploidies by FISH. Although there were significant differences in signal distribution, these did not lead to a different overall classification of the respective cases, i.e., the end results of disomic and trisomic cases for chromosome 18 were identical between FISH and PRINS. In 205 of 262 cases PRINS was performed for chromosomes X and Y. 97.6% of these samples were properly sex differentiated. CONCLUSIONS: The PRINS assay is a simple and cheap alternative to detect numerical aberrations of chromosome 18. However, the rate of false-positive results for chromosome X was calculated as 1% and the rate of false-negative ones for chromosome Y as 2%. Further investigations are required to transform PRINS into an alternative to conventional methods for routine rapid prenatal diagnosis of gonosomes.     

不育症患者精子X,Y及18染色体的荧光原位杂交分析

目的:分析不育症患者精子X,Y,18染色体的荧光原位杂交情况。方法:在男性不育症组中,2例无精子症患者从附睾抽吸获取精子、3例从睾丸获取精子、2例严重少精症患者从射出精液中找到精子。选择5例正常射出精液者作为对照组。应用荧光原位杂交法(FISH)检查精子X,Y以及18号染色体,比较两组精子染色体非整倍体的发生率。结果:不育症组睾丸精子、附睾精子的非整倍体率无差别,但不育症组精子与正常男性组精子比较,非整倍体总发生率、性染色体二体性率及缺对染色体率明显增高(2.8％vs0.58％,0.81％vs 0.19％,2.1％vs0.37％),P<0.001。结论:无精子症与严重少精子症患者的精子比正常精子具有更高的染色体非整倍体率,需要进行大样本的研究,为不育症患者的治疗和遗传咨询提供有效的证据。     

Chromosomal constitution of embryos derived from tripronuclear zygotes studied by fluorescence in situ hybridization using probes for chromosomes 4, 13, 18, 21, X, and Y

This study was designed to assess the chromosomal constitution and segregation patterns of cleaving embryos derived from tripronuclear zygotes. Thirty-two embryos obtained from 19 conventional IVF patients were analyzed by fluorescence in situ hybridization (FISH) using probes for chromosomes 4, 13, 18, 21, X, and Y. Sixteen embryos (50.0%) exhibited uniform, non-mosaic patterns. These embryos showed pure triploid (n = 7), pure diploid (n = 7), or pure haploid (n = 2). The remaining 16 embryos showed mosaic patterns; 1 was triploid-diploid mosaics, 9 were diploid-haploid, and 4 were haploid only. Autosomal aneuploidy occurred in 2 embryos showing a triploid complement. The sex chromosomal constituent XXX:XXY:XYY was 3:4:2 in embryos showing a pure triploid complement (including 2 embryos with aneuploidy). This ratio was not significantly different from the expected 1:2:1 (p = 0.96). Pure triploid was found in 41.7% of 2-cell embryos, but no triploid complement was found in 3-cell embryos. The present study also supports the diandric origin of tripronuclear zygotes in the conventional IVF, and, to our knowledge, is the first study to use simultaneous six-color FISH for chromosomes 4, 13, 18, 21, X, and Y in human embryos. However, no additive information was obtained about chromosome 4.     

Isodicentric Yp: prenatal diagnosis and outcome in 12 cases

OBJECTIVES: 1.To present the prenatal cytogenetic findings and postnatal outcome of 12 cases with an isodicentric chromosome composed of the short arm of the Y chromosome.2.To review the literature and provide recommendations for cytogenetic analysis and counseling. METHODS: Prenatal and postnatal cytogenetic data and clinical findings of isodicentric Yp ascertained in six institutions were gathered and reviewed. RESULTS: Nine of the twelve cases were referred for advanced maternal age (AMA), one of which was a twin pregnancy with one twin having an increased nuchal translucency measurement. The remaining cases were referred owing to a family history of hemophilia and an abnormal maternal serum screen, respectively. Nine of these pregnancies resulted in the birth of a normal-appearing male infant with subsequent normal growth and psychomotor development. Follow-up ranged from birth to 7 years. In two cases, the pregnancy was terminated and the fetuses showed male external genitalia. In the case ascertained because of an increased nuchal translucency measurement, the prenatal diagnosis of 45,X was made. At birth, there were ambiguous genitalia, and postnatal cytogenetic studies found an isodicentric Yp. In 11 of the 12 cases, mosaicism was present. CONCLUSION: Our cases show that the prenatal finding of an isodicentric Yp, with or without 45,X mosaicism, is compatible with normal male phenotype in most cases, particularly in the absence of other anomalies. To ensure accuracy in cytogenetic reporting and prenatal counseling, the identification of a structurally abnormal or small Y chromosome, either alone or in the presence of 45,X colonies, should be followed immediately by confirmatory molecular cytogenetic investigations as well as by ultrasound determination of the phenotypic sex of the fetus.     

Rapid detection of chromosomes X and Y aneuploidies by quantitative fluorescent PCR

Quantitative fluorescent polymerase chain reaction (QF-PCR) assays and small tandem repeat (STR) markers have been successfully employed for the rapid detection of major numerical aneuploidies affecting human autosomes. So far, the analysis of chromosomes X and Y disorders has been hampered by the rarity of highly polymorphic markers which could distinguish normal female homozygous PCR patterns from those seen in patients with Turner's syndrome. A new marker (X22) of the X/Y chromosomes has been identified which maps in the Xq/Yq pseudoautosomal region PAR2; used together with the HPRT it allows the rapid diagnosis of numerical aneuploidies of the sex chromosomes. Blood samples from normal male and female subjects and from patients with X and Y chromosome disorders (45,X and 47, XXY) have been tested by QF-PCR with the X22 polymorphic pentanucleotide (12 alleles) together with the HPRT and P39 markers. The samples were also tested by multiplex QF-PCR with STRs specific for chromosomes 21,18,13 and amelogenin (AMXY). Tested by QF-PCR, all samples from normal females were heterozygous for either the X22 or the HPRT marker with fluorescent peak ratios near 1:1, thus allowing a correct, rapid diagnosis of their chromosome complement. Turner's patients (45,X) showed only one X22 and one HPRT fluorescent peak, thus documenting the presence of a single X chromosome. Turner's patients with mosaicism showed a major fluorescent peak for the X22 and HPRT markers and a minor peak revealing the presence of a second minor population of cells. Two 47, XXY cases could also be diagnosed. Multiplex analyses can be performed using simultaneously STR markers for chromosomes 21,18,13 X and Y. The diagnostic value of a third X-linked marker (P39) was also investigated. These results suggest that rapid diagnosis of major numerical anomalies of the X and Y chromosomes can be performed using QF-PCR with a new highly polymorphic X-linked marker, X22, which maps in the Xq/Yq pseudoautosomal region PAR 2. Multiplex QF-PCR tests-using the X22 STR in association with HPRT and, in rare cases, a third P39 marker-allow the rapid diagnosis of major aneuploidies affecting chromosomes 21, 18, 13, X and Y. The X22 marker can also be employed for the detection of fetal cells present in maternal peripheral blood or the endocervical canal.     

Estimation of aneuploidy levels for 8, 15, 18, X and Y chromosomes in 97 human sperm samples using fluorescence in situ hybridization

Objective: To estimate the mean frequency of aneuploidy levels of chromosomes 8, 15, 18, X, and Y in human sperm, while minimizing the effect of individual factors by analyzing sperm samples from a large set of patients.

Design: Prospective randomized analysis of sperm nuclei by fluorescence in situ hybridization.

Setting: University-based laboratory for reproductive biology.

Patient(s): One hundred two patients with a large distribution of sperm parameters, randomly selected from volunteers who had presented seeking a semen analysis.

Intervention(s): The sperm samples were prepared for fluorescence in situ hybridization.

Main Outcome Measure(s): The disomy frequencies for chromosomes 8, 15, 18, and sex chromosomes were determined using fluorescence in situ hybridization.

Result(s): The mean frequencies of disomy for autosomes were 0.18% for chromosome 8, 0.06% for chromosome 15, 0.2% for chromosome 18, and 0.24% for gonosomes (XX, 0.04%; YY, 0.05%; XY, 0.15%).

Conclusion(s): This study confirms other previous evaluations on restricted numbers of patients. Our results seem to confirm a relative equiprobability of disomy frequencies concerning the different chromosomal pairs during male meiosis.     

Familial X centromere variant resulting in false-positive prenatal diagnosis of monosomy X by interphase FISH.

Interphase fluorescent in situ hybridization (FISH) analysis performed on uncultured amniotic fluid cells from a female fetus revealed a single signal using an X chromosome alpha-satellite probe, and the absence of any signal using a Y chromosome alpha-satellite probe. This result was initially interpreted as monosomy for the X chromosome in the fetus. Subsequent chromosome analysis from the cultured amniotic fluid cells showed two apparently normal X chromosomes. FISH using the X alpha-satellite probe on metaphase spreads revealed hybridization to both X chromosomes, although one signal was markedly reduced compared to the other. The same hybridization pattern was observed in the mother of the fetus. This is the first report of a rare familial X centromere variant resulting in a false-positive diagnosis of monosomy X by interphase FISH analysis for prenatal diagnosis.     

45,X/46,X,r(Y) karyotype transmitted by father to son after intracytoplasmic sperm injection for oligospermia. A case report.

BACKGROUND: The advent of assisted reproductive techniques, such as intracytoplasmic sperm injection (ICSI), has permitted conception and successful pregnancy for an increasing population of infertile men. Approximately 13.7% of infertile men with aspermia and 4.6% with oligospermia have a coexistent chromosome abnormality. Although the ICSI procedure appears safe thus far, early studies are in progress to evaluate outcomes of such pregnancies. For men whose infertility is linked to genetic conditions, it is an unprecedented challenge to predict the potential effects on their offspring. CASE: At 18 weeks' gestation, a 45,X/46,X,r(Y) karyotype was found on genetic amniocentesis performed for advanced maternal age. The pregnancy was achieved by ICSI using sperm from the husband, who was infertile due to severe oligospermia. Subsequently the same karyotype was found in the father. To our knowledge, this is the first reported case of familial transmission of ring Y chromosome. CONCLUSION: It is strongly recommended that ICSI and other new assisted reproductive techniques be preceded by genetic screening for male infertility as well as other indications warranted by the family history since traditional risk assessment may require revision and outcomes may be uncertain in some cases.