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Relevance of trisomy 15 and other chromosome abnormalities in spontaneous AKR leukemia of mice with and without Robertsonian rearrangement.

The types and frequencies of chromosomal abnormalities in spontaneous AKR leukemia are presented: 45% to 58% of leukemic animals exhibit chromosome abnormalities; trisomy of chromosome 15 (Ts 15) occurs as the predominant chromosome abnormality not only in AKR/J but also in two AKR sublines characterized by the presence of two or one Robertsonian biarmed translocation Rb (6.15) of the chromosomes 6 and 15. Most often a triplication of the whole Rb (6.15) is found in Rb (6.15) homozygotes corresponding to combined Ts 6 + Ts 15. In the Rb (6.15) heterozygotes both trisomy of the biarmed (6.15) and of the acrocentric 15 is observed. Centric fission of the (6.15) chromosome is also possible in Rb (6.15) homozygotes resulting in Ts 15 without simultaneous Ts 6. Trisomies of other chromosomes are found either in addition to Ts 15 or as the only abnormality. If the data of Dofuku et al. (1975) are considered, abnormal karyotypes in AKR leukemia show Ts 15 in 90%, Ts 12 and Ts 17 in 18%-20%, and Ts 3, Ts 10 and Ts 14 in 8%-10% of the cases.

AKR murine leukemia virus↗

Prenatal diagnosis of chromosomal abnormalities in women with high risk pregnancies.

BACKGROUND & OBJECTIVES: Prenatal diagnosis helps in averting the birth of infants with chromosomal abnormalities. Fluorescence in situ hybridization (FISH) has been introduced as a potentially powerful tool in clinical cytogenetics. Several studies have reported successful prenatal diagnosis of chromosomal abnormalities in high risk pregnancies using FISH, however there are no reported studies from an Indian set up. Prenatal diagnosis for the detection of chromosomal abnormalities was carried out by conventional cytogenetics in the present study in the foetuses of high risk pregnancies in women attending a tertiary care facility in north India. These cases were further analyzed using FISH, to test the efficiency and utility of this technique for prenatal detection of common aneuploidies. METHODS: A total of 82 women with high risk pregnancies (81 singleton, 1 twin) were included in the study. Prenatal diagnosis was performed in these women using conventional chromosomal analysis (CCA) and interphase or metaphase FISH on chorionic villus or amniotic fluid or cord blood samples. RESULTS: Chromosomal analysis was successful in 80 instances and uninformative in 2. Abnormal karyotypes were detected in five (6.09%) of these women. FISH was successful in all the subjects and the results were in conformity to the cytogenetic results. In the 2 women where cytogenetic analysis was uninformative, results were given on the basis of interphase FISH. INTERPRETATION & CONCLUSION: The study clearly demonstrates that prenatal diagnosis is useful in the detection of chromosomal abnormalities in foetuses of women with high risk pregnancies. FISH is a powerful sensitive molecular cytogenetic technique, through which specific chromosomal abnormalities can be diagnosed/identified rapidly and accurately and may be used as an adjunct to conventional cytogenetic analysis.

Adult↗

Ultrasound-adjusted risk and spectrum of fetal chromosomal abnormality in women with elevated maternal serum alpha-fetoprotein.

OBJECTIVE: To determine the incidence of chromosomal abnormality in sonographically normal fetuses after amniocentesis for elevated maternal serum alpha-fetoprotein (MSAFP), and to compare the spectrum of abnormality with that seen in women undergoing amniocentesis for advanced maternal age. METHODS: Cytogenetic and sonographic findings from women undergoing amniocentesis for elevated MSAFP (at least 2.0 multiples of median) between 1988-1992 were reviewed retrospectively. The literature was reviewed and data compiled regarding the risk of chromosomal abnormality for women with elevated MSAFP levels. RESULTS: The incidence of abnormal karyotype among all women with elevated MSAFP was 1.23% (nine of 733). The risk of an abnormal karyotype with a normal ultrasound examination was 1.01% (seven of 696). This included three fetuses with sex chromosome abnormalities, three with de novo, apparently balanced rearrangements, and one with an unbalanced structural rearrangement. CONCLUSIONS: The risk of chromosomal abnormality in nonselected patients, predominantly younger than 35 years of age, with elevated MSAFP and a sonographically normal fetus is 0.6%, based on a compilation of our data and reports published previously. The spectrum of abnormality in women with elevated MSAFP differs from that in women of advanced maternal age. Patients should be specifically counseled regarding this difference.

Adult↗

In vitro fertilization plus preimplantation genetic diagnosis in patients with recurrent miscarriage: an analysis of chromosome abnormalities in human preimplantation embryos.

OBJECTIVE: To analyze the incidence of numeric chromosomal abnormalities in preimplantation embryos from women with unexplained recurrent miscarriage (RM) so as to seek an etiology and to determine whether the use of IVF may be indicated to treat these cases. DESIGN: Prospective controlled study. SETTING: University laboratory of reproductive genetics and a tertiary referral center for infertility. PATIENT(S): Nine women with a mean (+/-SD) of 3.9 +/- 0.6 RMs who were undergoing IVF and preimplantation genetic diagnosis, and a control group of young (n = 10) and older (n = 6) patients who were undergoing preimplantation genetic diagnosis because of sex-linked diseases. INTERVENTION(S): In vitro fertilization, embryo culture for 72 hours, blastomere biopsy, and analysis of chromosomes 13, 16, 18, 21, 22, X, and Y with the use of fluorescent in situ hybridization. Transfer of chromosomally normal embryos into the uterus. MAIN OUTCOME MEASURE(S): Numeric chromosomal abnormalities in human embryos. RESULT(S): Sixty-six embryos from patients with RM were compared with 62 embryos from young patients and 41 embryos from older patients. There was a significant increase in the rate of abnormal embryos in the patients with RM and the older patients compared with the controls. Abnormalities in most of the chromosomes studied were higher in the RM group than in the control group, especially those affecting chromosome 13. CONCLUSION(S): There was an increase in numeric chromosomal abnormalities in preimplantation embryos from women with RM that could be the cause of infertility in many couples with unexplained RM. The use of IVF in such circumstances may be indicated if successful preimplantation genetic diagnosis is added to the procedure.

Abortion, Habitual↗

Frequencies of fetal chromosomal abnormalities at prenatal diagnosis: 10 years experiences in a single institution.

We present frequencies of fetal chromosomal abnormalities in 4,907 prenatal cytogenetic examinations at Samsung Cheil Hospital from 1988 to 1997 for 10 yr duration. Prenatal karyotypes were undertaken in 3,913 amniotic fluid samples, 800 chorionic villi samples, and 194 percutaneous umbilical blood samples. The frequency of fetal abnormal karyotypes was 3.1% (150 cases). Numerical chromosome abnormalities were 87 cases (1.8%) and structural aberrations of chromosomes were 63 cases (1.3%). In the numerical chromosomal abnormalities, the frequency of trisomy 21 was by far the highest (36 cases), followed by trisomy 18 in 22 cases and sex chromosome aneuploidies in 19 cases. In the structural chromosomal aberrations, 5 cases had the inversions in chromosome 2, 7, 17, and Y. Chromosomal deletions in 6 cases and additions in 4 cases were analysed. Of the remaining 47 translocation in abnormal fetuses, reciprocal translocation was in 26 cases and Robertsonian translocation in 21 cases. Among them, 41 cases were balanced translocation and 6 were unbalanced. Thirty five cases of translocation were inherited from one of the parents. Four had de novo chromosome rearrangements, and 8 cases were unknown.

Chromosome Aberrations↗

Trisomy 13: a new recurring chromosome abnormality in acute leukemia.

A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias.

Acute Disease↗

The role of ductus venosus blood flow assessment in screening for chromosomal abnormalities at 10-16 weeks of gestation.

OBJECTIVE: To evaluate the role of ductus venosus blood flow assessment at 10-16 weeks' gestation in screening for chromosomal abnormalities. METHODS: Ductus venosus blood flow was prospectively evaluated in 1371 consecutive pregnancies between 10 and 16 weeks of gestation. The pulsatility index for veins was calculated. All cases were screened for chromosomal defects combining maternal age and fetal nuchal translucency thickness. RESULTS: A chromosomal abnormality was found in 20 cases. The overall detection rate, specificity, positive predictive value, negative predictive value and odds ratio for chromosomal abnormalities were 65%, 95.7%, 18.3%, 99.5% and 41 (95% CI 16-108), respectively, when using the 95th centile pulsatility index as a cut-off. CONCLUSIONS: These preliminary results suggest that evaluation of the ductus venosus pulsatility index at 10-16 weeks' gestation is a useful second-line screening test for chromosomal defects. A combination of nuchal translucency measurement and ductus venosus assessment might increase specificity while maintaining an optimal detection rate for chromosomal abnormalities. Such a policy could identify 55% of all chromosomal abnormalities and about 69% of autosomal trisomies, reducing the need for invasive testing to less than 1%.

Adult↗

Nuchal translucency: an ultrasound marker for fetal chromosomal abnormalities.

CONTEXT: The literature shows an association between several ultrasound markers and chromosome abnormality. Among these, measurement of nuchal translucency has been indicated as a screening method for aneuploidy. The trisomy of chromosome 21 has been most evaluated. OBJECTIVE: To define the best fixed cutoff point for nuchal translucency, with the assistance of the ROC curve, and its accuracy in screening all fetal aneuploidy and trisomy 21 in a South American population. TYPE OF STUDY: Validation of a diagnostic test. SETTING: This study was carried out at the State University of Campinas, Campinas, Brazil. PARTICIPANTS: 230 patients examined by ultrasound at two tertiary-level private centers, at 10 to 14 weeks of gestation. DIAGNOSTIC TEST: The participants consisted of all those patients who had undergone ultrasound imaging at 10 to 14 weeks of gestation to measure nuchal translucency and who had had the fetal or neonatal karyotype identified. MAIN MEASUREMENTS: Maternal age, gestational age, nuchal translucency measurement, fetal or neonatal karyotype. RESULTS: Prevalence of chromosomal defects - 10 %; mean age - 35.8 years; mean gestational age - 12 weeks and 2 days; nuchal translucency (NT) thickness - 2.18 mm. The best balance between sensitivity and specificity were values that were equal to or higher than 2.5 mm for overall chromosomal abnormalities as well as for the isolated trisomy 21. The sensitivity for overall chromosomal abnormalities and trisomy 21 were 69.5 % and 75 %, respectively, and the positive likelihood ratios were 5.5 and 5.0, respectively. CONCLUSION: The measurement of nuchal translucency was found to be fairly accurate as an ultrasound marker for fetal abnormalities and measurements equal to or higher than 2.5 mm were the best fixed cutoff points.

Adult↗

Comprehensive chromosomal abnormality detection: integrating CNV-Seq with traditional karyotyping in prenatal diagnostics.

BACKGROUND: This study aimed to evaluate the efficacy of copy number variation sequencing (CNV-Seq) in detecting chromosomal abnormalities in prenatal diagnosis, comparing its performance with traditional karyotype analysis. METHODS: A retrospective analysis was conducted on 1001 prenatal samples collected between April 2021 and December 2023. Samples were analyzed using both CNV-Seq and karyotype analysis. The detection rates of chromosomal abnormalities were compared between the two methods across various prenatal diagnostic indications. Clinical follow-up was performed to assess pregnancy outcomes. RESULTS: CNV-Seq detected chromosomal abnormalities in 89 of 1,001 cases (8.9%), compared to 50 cases (5.0%) identified by traditional karyotyping. CNV-Seq not only detected all abnormalities identified by karyotyping, including common aneuploidies such as trisomy 21 and sex chromosome abnormalities, but also uncovered 53 additional pathogenic submicroscopic CNVs associated with 33 known syndromes. The detection rates of CNV-Seq were significantly higher in high-risk groups, such as those identified by non-invasive prenatal testing (HR-NIPT) and maternal serum screening (HR-MSS), demonstrating superior sensitivity and accuracy in prenatal diagnostics. CONCLUSION: CNV-Seq demonstrated superior sensitivity in detecting chromosomal abnormalities, particularly submicroscopic alterations, compared to traditional karyotyping. The study highlights the potential of CNV-Seq as a valuable tool in prenatal diagnostics, offering improved detection of genetic abnormalities and guiding clinical decision-making. However, a combined approach using both CNV-Seq and karyotype analysis is recommended for comprehensive prenatal genetic screening.

Humans↗

A role for maternal serum screening in detecting chromosomal abnormalities in fetuses with isolated choroid plexus cysts: a prospective multicentre study.

A prospective multicentre study was performed to identify patients with fetal choroid plexus cysts and examine the association between choroid plexus cysts and chromosome abnormalities in the context of variables such as maternal age, serum triple-screen results, race, other prenatally-identified fetal anomalies and cyst characteristics. A total of 18 437 scans were performed in 5 centres and 257 fetuses were identified with choroid plexus cysts. Outcome was available on 250 patients, and of these, chromosomal abnormalities were detected in a total of 13 (5.2 per cent) fetuses. 26 patients in the group had additional ultrasound abnormalities, and 8 of these had fetal chromosome abnormalities. Among the 224 patients with isolated choroid plexus cysts, 5 (2.2 per cent) were found to have chromosomal abnormalities. All cases with identified chromosomal abnormalities were associated with an additional risk factor, such as other ultrasound findings, advanced maternal age or abnormal maternal serum triple-screen results.

Adolescent↗

[Detection of common chromosome abnormalities in myelodysplastic syndrome with a panel fluorescence in situ hybridization].

OBJECTIVE: To evaluate the value of a panel fluorescence in situ hybridization (FISH) in the detection of common chromosome abnormalities in myelodysplastic syndrome (MDS). METHODS: Twenty cases of MDS patients, whose karyotypes were unknown by the FISH examiner beforehand, were analyzed with a panel FISH using YAC248F5 (5q31), YAC938G5 (7q32), CEP8 and YAC 912C3 (20q12) probes to detect the frequently occurring chromosome abnormalities (-5/5q, -/7q-, +8, 20q-) in MDS. Then the results were compared to those of conventional cytogenetics (CC). RESULTS: Among 20 cases, 13 cases were found to carry common chromosome abnormalities by panel FISH (trisomy 8, five cases; -5/5q-, one case; 20q-, five cases; 5q- accompanying 20q-, one case; complex abnormalities, one case). However, on CC examination, only five cases were found to have common chromosomal abnormalities (20q-, four cases; 5q- accompanying 20q-, one case). In addition, trisomy 21, marker chromosome and complex abnormalities comprising -5, -7 and marker chromosomes were seen in one case each, the rest were normal. CONCLUSION: Panel FISH is a useful tool of molecular cytogenetics in the detection of common chromosome abnormalities in MDS.

Adult↗

First-trimester nuchal translucency: a risk analysis on fetal chromosome abnormality.

PURPOSE: To investigate the importance of nuchal translucencies in the first trimester of pregnancy as an ultrasonographic marker for fetal chromosome abnormalities. MATERIALS AND METHODS: One hundred two first-trimester fetuses with a nuchal translucency of 3 mm or more were karyotyped. Multiple logistic regression analysis was performed to estimate the risk of fetal chromosomal abnormalities related to nuchal translucencies. RESULTS: Fifty-five (54%) of the fetuses had a normal karyotype. Forty-seven (46%) had an abnormal karyotype. The risk of chromosome abnormality was strongly increased in fetuses with a septated nuchal translucency compared with fetuses with a nonseptated nuchal translucency. CONCLUSION: First-trimester nuchal translucency is an important ultrasonographic marker for chromosomal abnormalities in the fetus. The presence of a normal karyotype in a fetus is a strong indication that detailed ultrasonographic examination for associated anomalies should be undertaken.

Adult↗

The presence of multinucleated blastomeres in human embryos is correlated with chromosomal abnormalities.

The purpose of the present study was to determine whether the presence of one or more multinucleated blastomeres during early embryonic development is associated with chromosomal abnormalities in sibling blastomeres of that embryo. Embryos with multinucleated cells (n = 47) detected on day 2 or 3 or development were compared to dividing embryos without multinucleation. Arrested embryos were excluded from this study. Chromosome abnormalities were detected using fluorescent in-situ hybridization (FISH) with X, Y, 18 and 13/21 chromosome-specific probes. Of 47 embryos included in this study, 76.6% were chromosomally abnormal, compared to 50.9% in the control group (P < 0.001). Excluding aneuploidy, which is originated in the gametes and not the embryo, the differences were even higher, with 74.5% of multinucleated embryos being chromosomally abnormal compared to 32.3% of non-multinucleated embryos (P < 0.001). Day of multinucleation appearance, number of nuclei per cell, number of multinucleated cells per embryo and developmental quality of the embryos as well as the type of fertilization (intracytoplasmic sperm injection versus standard insemination) were not found to affect the rate of chromosomal abnormalities in embryos with multinucleated cells. These results suggest that embryos with multinucleated cells may not be suitable for replacement and should be excluded unless no other embryos are available.

Blastomeres↗

Chromosome abnormalities in human arrested preimplantation embryos: a multiple-probe FISH study.

Numerical chromosome abnormalities were studied in single blastomeres from arrested or otherwise morphologically abnormal human preimplantation embryos. A 6-h FISH procedure with fluorochrome-labeled DNA probes was developed to determine numerical abnormalities of chromosomes X, Y, and 18. The three chromosomes were stained and detected simultaneously in 571 blastomeres from 131 embryos. Successful analysis including biopsy, fixation, and FISH analysis was achieved in 86.5% of all blastomeres. The procedure described here offers a reliable alternative to sexing of embryos by PCR and allows simultaneous ploidy assessment. For the three chromosomes tested, numerical aberrations were found in 56.5% of the embryos. Most abnormal embryos were polyploid or mosaics, and 6.1% were aneuploid for gonosomes or chromosome 18. Extrapolation of these results to all human chromosomes suggests that the majority of abnormally developing and arrested human embryos carry numerical chromosome abnormalities.

Adult↗

[Chromosomal abnormalities and their clinical significance in acute lymphoblastic leukemia in adults].

To determine the chromosomal abnormalities and their clinical significance in adult acute lymphoblastic leukemia, karyotypic analyses with R- and/or G-banding were performed in 101 newly diagnosed ALL patients. The results showed that 69 (68.32%) cases had clonal chromosomal abnormalities and specific abnormalities including Philadelphia chromosome (32.67%), t(4;11) (2.97%), t(11;14) (3.96%), abnormalities of 8q24 (2.97%), 6q- (4.96%). Patients with Ph chromosome showed higher leukocyte counts and more frequent hepatosplenomegaly and most of them were L2 and B lineage subtypes. They had lower complete remission (CR) rate, needed longer time to achieve CR and relapsed earlier as compared with patients without Ph chromosome. These suggested that chromosomal abnormalities are very frequent and some specific abnormalities had specific clinical features.

Adolescent↗

Developmental competence of porcine parthenogenetic embryos relative to embryonic chromosomal abnormalities.

Parthenogenetically activated (PA) embryos exhibit delayed development, a lower blastocyst rate, and less successful development in vitro compared to in vitro fertilized (IVF) embryos. To investigate the possible mechanisms for unsuccessful parthenogenetic development, this study analyzed the chromosome abnormalities and developmental potential of porcine PA embryos. Mature oocytes were electrically activated and cultured in Porcine Zygote Medium-3 (PZM3) supplemented with 3 mg/ml BSA for 6, 7, or 8 days. The percentage of PA blastocysts was lower than that of IVF embryos on days 6 and 7 (16.4 +/- 7.4 vs. 28.7 +/- 3.7; 10.9 +/- 2.8 vs. 21.5 +/- 4.7, P < 0.05; respectively), and the PA blastocysts had significantly fewer nuclei than IVF blastocysts (23.2 +/- 1.8 vs. 29.7 +/- 0.8; 29.7 +/- 3.3 vs. 32.0 +/- 2.4, P < 0.05). The percentage of abnormal PA embryos (including embryos with condensed nuclei, arrested embryos and fragmented embryos) was higher than that of IVF embryos (PA: 52.9 +/- 12.8 vs. 16.4 +/- 7.4 on day 6), and increased with culture time (71.9 +/- 12.1 vs. 10.9 +/- 2.8. on day 7,and 75.0 +/- 22.6 vs. 12.1 +/- 2.3 on day 8, P < 0.05). The Day-6 PA blastocysts (n = 147) were divided into three classes according to the total number of nuclei (<20, 20-39, >40) and into three groups according to the morphological diameter (<150, 150-180, >180 microm). Of the haploid blastocysts, 56.1% had less than 20 nuclei, and 71.5% were less than 150 microm in diameter. Of all (114) blastocysts suitable for analysis, 55.5% displayed chromosomal abnormalities. Among chromosomal abnormalities in PA blastocysts, haploid blastocysts were most prevalent (43.6%), while polyploidy (4.4%) and mixoploidy (7.7%) embryos were less prevalent. Chromosomal abnormalities of porcine PA embryos might contribute to a higher rate of abnormal embryonic development. We suggest that a careful consideration should be given when using the blastocysts with smaller size, and establishing the optimum culture condition for PA embryos development in vitro.

Animals↗

Chromosomal abnormalities in a clinic sample of individuals with autistic disorder.

We examined data from the largest reported sample of autistic individuals who have been karyotyped with the aim of providing additional information in the search for autism disease genes. Individuals seen in the University of Iowa's Child and Adolescent Psychiatry Clinic since 1980 who had been diagnosed with autism were cross-referenced with the University of Iowa's Cytogenetics Laboratory database. We determined the number of individuals referred for cytogenetic testing and, of these, the number found to have gross cytological abnormalities. Medical records were reviewed for all cases with such abnormalities. Between 1980 and 1998, 898 subjects seen in the clinic were diagnosed with autism. Of these, 278 (30.1%) were referred for cytological studies; 25 (9.0%) of these were found to have chromosomal abnormalities. The most common chromosomal abnormalities were Fragile X, other sex chromosome anomalies, and chromosome 15 abnormalities. These data support the contribution of chromosomal abnormalities to a small but significant number of cases of autism, and highlight the involvement of chromosome 15 and the sex chromosomes.

Abnormalities, Multiple↗

Cystic fibrosis and chromosome abnormalities associated with echogenic fetal bowel.

OBJECTIVE: To determine the prevalence of cystic fibrosis mutations and chromosome abnormalities in the fetuses of a heterogeneous population of pregnant women referred for prenatal testing for echogenic fetal bowel. METHODS: Fetal or parental samples obtained after a second-trimester sonographic finding of echogenic fetal bowel were submitted to a referral diagnostic laboratory during a 2-year period. Results of DNA testing and karyotyping on these samples were analyzed to determine the prevalence of cystic fibrosis transmembrane reductase gene mutations and chromosome abnormalities. RESULTS: Of 244 cases tested, two fetuses were positive for two cystic fibrosis mutations. This rate (0.8% or two of 244) is 20 times higher than the general white population rate of one per 2500. In a third case, both parents were carriers but the fetus was not tested. Nine (8%) of 113 fetuses tested had one cystic fibrosis mutation. Of 106 fetuses for whom chromosome results were available, three (2.8%) fetuses had a chromosomal abnormality: two had trisomy 21 and one had Klinefelter syndrome. A fourth fetus carried a de novo, apparently balanced, 5;12 translocation. CONCLUSION: These laboratory results are representative of a broad spectrum of clinical settings and indicate a generalized increased risk associated with this sonographic finding. Therefore, when a second-trimester sonographic diagnosis of fetal echogenic bowel is made, fetal testing for both cystic fibrosis and chromosome abnormalities is warranted.

Adult↗