Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML), which is a disease with Philadelphia(Ph) chromosome as the major abnormality. In the present study, we report a 76-year-old patient suspected of having AML with eosinophilic differentiation (AML-M4), which in clinical tests resembles CML blast crisis with multiple chromosomal abnormalities. Isochromosome 21 [i(21)(q10)] was the most recurrent feature noted in metaphases with 46 chromosomes. Ring chromosome, tetraploid endoreduplication, recurrent aneuploid clones with loss of X chromosome, monosomy 17, monosomy 7, and structural variation translocation (9;14) were also observed in this patient. Fluorescent in situ hybridization (FISH) confirmed the absence of Ph chromosome. This report shows how cytogenetic analyses revealed atypical structural aberrations in the M4 subtype of AML.
Aged ; Blast Crisis ; genetics ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 14 ; genetics ; Chromosomes, Human, Pair 17 ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; Chromosomes, Human, X ; genetics ; Cytogenetic Analysis ; Endoreduplication ; Humans ; In Situ Hybridization, Fluorescence ; Isochromosomes ; Leukemia, Myelomonocytic, Acute ; genetics ; pathology ; Male ; Philadelphia Chromosome ; Polyploidy ; Ring Chromosomes ; Translocation, Genetic

The toxic action of benzene on erythropoiesis and myelopciesis, has been recognized since the early years of the present century. With the advance in high civilization and modern covenience, benzene as a kind of aromatic compound has been used for industrial solvent and its longstanding use has committed a public nuisance to be overcome by medical approach. Chromosomal breakage and rearrangement may be produced by radiation, radiomimetics, virus infection and various chemicals, especially, antibiotics and antitumor agent, causing chroimosomal rearrangement in vitro, whose teratogenic action in rats was previously demonstrated. Several works hsve been published on the chromosome damage as a consequence of benzene intoxication. Recently, it was shown by certain workers that individuals who had been exposed to atmospheric benzene, even without haematological disorders, might have an elevated percentage of structural chromosome aberrations in the lymphocytes cultured from their peripheral blood. Moreover, structural and numerical chromosome aberrations were demons trated in patients with blood disorders which were believed to be due to exposure to beuzene vapors. Accordingly, much interest has been paid to its cytologic effect on the hematopoietic tissues in man and experimental animals. A high incidence of chromosomal aberrations has also been found in rabbits exposed to benzene during a period of peripheral pancytopenia and after hematologic recovery. The significance of these findings was discussed in relation to leukemic transition and to their diagnostic value in human benzene intoxication. Chromosomal anomalies can also be induced by benzene given subcutaneously to rata. A pronounced individual variation of the degree of chromosome damage was shown. The purpose of this investigation was to determine whether benzene could a direct effect on the chromosome complement of mammalian bone marrow cells in vivo and whether characteristic banding patterns might be demonstrated in rat chomosomes by a modified trypsin-Giemsa method. Four-week old Sprague-Dawley strain rats of both sexes(each weighing about 50gm) were used for this experimental study. Three groups of animals were treated-with subcutaneous infections of pure benzene. Group I received benzene, 2.0ml per kg body weight, 24 hours before sacrifice; Group II, 48 and 24 hours and Group III, 72, 48 and 24 hours. A control group was given no treatment. The animais were sacrificed in ether anesthesia. Femur and iliac bone marrow cells were suspended in medium 199 within 30 minutes and transferred to warm Hanks-distilled water(1:3) for hypotonic treatment(10 minutes). A freshly prepared solution of methanol glacial acetic acid (3:1) was used as fixative. Finally, a few drops of the cell suspension were placed on moistened, pre-cleaned slides being dried by rapid-drying technique. The slides were stained with either simple Giemsa or trypsin Giemsa banding technique. From the data obtained, this report was summarized as follows: 1. For the benzene-treated groups, chromosomal aberration rate was 13.4% in group II and 38.6% in group III, while in the controls the rate was 6.4 percent. 2. Numerical aberrations included aneuploidy, polyploidy and monoploidy. The most frequent type was hypodiploidy (5.8–9.4%) in all the treated groups. 3. Structural aberrations could be divided in gaps, ring chromosomes, breaks, deletions, exchanges and dicentrics. Among those, the majority of abnormal metaphases was gaps; 2.4%, 2.2% and 10.8% in group I, II and III respectively, and 1. 6% in control group. 4. The translocations and dicentrics were not demonstated in group I and II. 5. The normal chromosome set of the Sprague-Dawley rat was comprised of 42 chromosomes: 20 pairs of autosomes, and one pair of sex chromosomes, xx or XY chromosomes. The total number of major bands in s chromosome complement was about 40 and minor bands, 13, 6. Sucessful demonstration of banding patterns was available by proper adjustment of the concentration, temperature and duration of trypsin solution.
Acetic Acid ; Anesthesia ; Aneuploidy ; Animals ; Anti-Bacterial Agents ; Benzene ; Body Weight ; Bone Marrow Cells ; Bone Marrow ; Chromosome Aberrations ; Chromosome Breakage ; Civilization ; Complement System Proteins ; Erythropoiesis ; Ether ; Femur ; Humans ; In Vitro Techniques ; Incidence ; Lymphocytes ; Methanol ; Methods ; Pancytopenia ; Polyploidy ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Ring Chromosomes ; Sex Chromosomes ; Trypsin

Monosomic karyotype (MK) has recently been associated with poor prognosis of myelodysplastic syndromes (MDS). The objective of the current study was to investigate the prevalence and spectrum of autosomal monosomies in an unselected cohort of patients with known or suspected MDS by using retrospective analysis. The results showed that bone marrow cytogenetic studies (1532 cases) were performed between 2004 and 2012, and an abnormal karyotype was found in 538 cases (35.1%). In the 538 cases, 202 (37.5%) cases had autosomal monosomies including sole (n = 47, 23.3%), part of two (n = 33, 21.3%) or more (n = 122, 78.7%) anomalies. Almost all 22 autosomes were involved, but monosomy 7 was by far the most frequent, constituting 66.1% of all isolated monosomies and the highest fraction of those with two or more abnormalities. Other recurrent sole monosomies included chromosomes 20 (15.0%) and 13 (8.5%). Monosomy 13 (12.5%), 18 (8.3%), 20 (6.3%), 17 (7.3%), 21 (5.2%), 5 (5.2%) and 12 (5.2%) were also recurrent in the setting of 3 abnormalities. Bone marrow histology and clinical information were reviewed in all cases with isolated monosomy; associated clinical phenotypes were found in RCMD (n = 20, 13 were -7), RAEB (n = 12, 11 were -7), RA (n = 9, 3 were -7) and chronic myelomonocytic leukemia (CMML, n = 6, 4 were -7) cases. Sole monosomy 20 (n = 7, RA 3 case and RCMD 4 cases) was not detected in RAEB or CMML cases. It is concluded that the presence of at least 1 autosomal monosomy was documented in approximately 37.5% of all abnormal cases, which has potential impact on a more than trivial fraction of patients with MDS. The preponderance of monosomy 7 implicates a pathogenetic role for haploinsufficiency of genes associated with chromosome 7. The rarity of sole monosomy involving other chromosomes other than 7, 20, and 13 suggests that haploinsufficiency involving entire chromosomes is detrimental to cell survival, unless their effect is overcome by the presence of other genetic changes that are often associated with additional chromosomal abnormalities. The observation is consistent with the usually favorable prognostic profile associated with sole monosomy 20.
Abnormal Karyotype ; Chromosome Aberrations ; Chromosome Deletion ; Humans ; Karyotyping ; Monosomy ; Myelodysplastic Syndromes ; genetics ; Prognosis ; Retrospective Studies

BACKGROUND: Growth retardation (GR) has literally hundreds of causes that have differences in prognoses, complications, and responses to treatments. Especially, growth retarded patients resulting from chromosomal disorders should be genetically counseled. To focus the cytogeneticist's attention on specific chromosomal regions, it is important to understand cytogenetic aberrations associated with GR prior to chromosomal analysis. So, we attempted to figure out the cytogenetic findings of patients with GR and support the effective application of cytogenetic studies, accurate diagnosis and genetic counseling. METHODS: Of 203 cases referred for GR, the positive rate and pattern of chromosomal aberrations were retrospectively analyzed with review of associated clinical features. Cytogenetic studies were performd by high resolution banding technique after peripheral T lymphocyte culture and, if necessary, Ag-NOR stain, C-banding and fluorescence in situ hybridization. RESULTS: Forty two (20.7%) patients had abnormal karyotypes. Thirty one (15.2%) patients had well-recognized chromosomal syndromes including Turner, Cri-du-chat, Edward, 13q- and 18p-/ 18q- syndromes. In addition to those, the sporadic chromosomal aberrations of 11 cases were partial monosomy of 11q23, partial trisomy of 1q32, 4p, 9p, and 14q, and ring chromosome 4 and 18, etc. which were not literally established in view of the correlation with phenotype. CONCLUSIONS: The various results of definite or debating chromosomal disorders associated with GR could be used as the data for diagnosis, management, prognosis, and genetic counseling in growth retarded patients. Furthermore, these may provide the background for prospective study to define the new chromosomal disorders.
Abnormal Karyotype ; Chromosome Aberrations* ; Chromosome Deletion ; Chromosome Disorders ; Cytogenetics* ; Diagnosis ; Fluorescence ; Genetic Counseling ; Humans ; In Situ Hybridization ; Lymphocytes ; Phenotype ; Prognosis ; Retrospective Studies ; Ring Chromosomes ; Trisomy

PURPOSE: Cytogenetic analysis of spontaneous abortions (SABs) provides valuable information to establish the causes of fetal loss, information that is essential to provide accurate reproductive and genetic counseling couples. Such analysis also provides information on the frequencies and types of chromosomal abnormalities and associated risks of recurrence. However, there have only been a few reports of chromosomal abnormalities in small samples of SABs in the Korean population. Here, we report the incidence and spectrum of chromosomal abnormalities for cases of 470 SAB in Korea. MATERIALS AND METHODS: Between 2005 and 2010, a total of 470 products of conception (POC) resulting from SABs were submitted to our laboratory for cytogenetic analysis from various medical sites in Korea. The incidences and types of specific chromosomal abnormalities were determined. The abnormalities were distinguished by gestational age at the time of SAB and by maternal age. RESULTS: The frequency of chromosomal abnormalities in POCs was 54.3% (255/470), including 228 (89.3%) numerical and 27 (10.7%: 3 balanced and 24 unbalanced) structural abnormalities. Among the numerical abnormalities, trisomy was predominant (67.0%), followed by monosomy X (12.5%), polyploidy (8.2%), triple X (0.8%), and autosomal monosomy (0.8%). The overall sex ratio (male: female) among the 470 POCs with normal and abnormal karyotypes were 0.58 and 0.65, respectively. Trisomies were identified for each autosome, with the exceptions of 1, 3, and 19. Among the 171 autosomal trisomies, trisomy 16 was the most common (19.9%), followed by trisomy 22 (13.5%), trisomy 21 (12.3%), trisomy 15 (9.9%), and trisomies 18 and 13 (5.3%). The frequency of chromosomal abnormalities decreased with gestational age and increased with maternal age, but only because of increases in trisomies and complex abnormalities. CONCLUSIONS: We have presented a large collection of cytogenetic data for SABs collected during the past 6 years and provided a database for prenatal genetic counseling of parents who have experienced SABs in Korea.
Abnormal Karyotype ; Abortion, Spontaneous ; Chromosome Aberrations ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 22 ; Cytogenetic Analysis ; Cytogenetics ; Down Syndrome ; Family Characteristics ; Female ; Fertilization ; Genetic Counseling ; Gestational Age ; Humans ; Incidence ; Karyotype ; Korea ; Maternal Age ; Monosomy ; Mosaicism ; Parents ; Polyploidy ; Pregnancy ; Recurrence ; Sex Ratio ; Trisomy

Triplication of 1q is a very rare chromosomal abnormality in hematologic malignancies, and it has been related to Fanconi anemia. The clinical significance of this abnormality is unknown. We report here on a 55-year-old female patient who had myelodysplastic syndrome (refractory anemia with excess blasts) with triplication of 1q and trisomy 8 as the clonal cytogenetic abnormalities, as determined by bone marrow cytogenetic analysis. However, there were no clinical manifestations of Fanconi anemia or any chromosomal instability according to the peripheral blood chromosomal breakage testing. The patient developed early gastric carcinoma (poorly differentiated adenocarcinoma with a signet ring cell component) eight months later. She continuously had pancytopenia with dysplastic features, but this showed no evidence of evolving to leukemia or any relapse of the gastric carcinoma over a 2 year follow up.
Adenocarcinoma ; Anemia ; Bone Marrow ; Chromosomal Instability ; Chromosome Aberrations ; Chromosome Breakage ; Cytogenetic Analysis ; Fanconi Anemia ; Female ; Follow-Up Studies ; Hematologic Neoplasms ; Humans ; Leukemia ; Middle Aged ; Myelodysplastic Syndromes* ; Pancytopenia ; Recurrence ; Trisomy

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.
Animals ; Child, Preschool ; Chromosome Aberrations ; Chromosome Deletion ; Congenital Abnormalities ; genetics ; Epigenesis, Genetic ; Female ; Genomic Imprinting ; HIV Infections ; transmission ; Haploidy ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Infertility, Male ; genetics ; Klinefelter Syndrome ; genetics ; Male ; Pregnancy ; Preimplantation Diagnosis ; Risk ; Sex Chromosome Aberrations ; Sperm Injections, Intracytoplasmic ; adverse effects ; Spermatogenesis ; genetics ; Translocation, Genetic ; genetics ; X Chromosome ; genetics ; XYY Karyotype ; genetics

OBJECTIVE: To explore the clinical effect of expanded non-invasive prenatal testing (NIPT-plus) for prenatal screening. METHODS: The screening result, prenatal diagnosis and pregnancy outcome of 3700 pregnant women who volunteered NIPT-plus screening at our center from September 2018 to December 2019 were reviewed. RESULTS: Among the 3700 pregnant women, 74(2.0%) were scored positive for clinically significant fetal chromosomal abnormalities and underwent NIPT-plus screening. Sixty three women with a high risk underwent invasive prenatal diagnosis, among whom 19 were diagnosed, which yielded a positive predictive value (PPVs) of 30.2% (19/63). Statistical analysis showed that NIPT-plus has higher PPVs for common aneuploidies and low-to-medium PPVs for sex chromosome aneuploidies and microdeletion/microduplication syndromes. CONCLUSION As a screening technique, NIPT-plus has broader applications compared with conventional techniques, and has reference value for clinicians and pregnant women during pregnancy.
Aneuploidy ; Chromosome Aberrations ; Female ; Humans ; Pregnancy ; Pregnancy Outcome ; Prenatal Diagnosis ; Sex Chromosome Aberrations

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus

OBJECTIVE: To analyze the indication, karyotyping result, ultrasound finding, pregnancy decision and follow-up of fetuses with sex chromosome aneuploidies (SCA) detected by non-invasive prenatal testing (NIPT) during early and midterm pregnancies. METHODS: The results of 225 singleton pregnancies with fetal SCA detected by NIPT were reviewed and analyzed. RESULTS: The 225 cases included 45,X (n=37), 47,XXY (n=74), 47,XXX (n=50), 47,XYY (n=56) and mosaicisms (n=8), among which 121 (53.8%) have opted to terminate the pregnancy, including 45,X (n=31), 47,XXY (n=61), 47,XXX (n=14), 47,XYY (n=12) and 3 mosaicisms. The remainder 104 (46.2%) have elected to continue with the pregnancy, among which three have opted to terminate due to abnormalities detected by ultrasonography, and two had spontaneous abortions. CONCLUSION NIPT as a first-tier screening method can effectively detect fetal trisomies 21, 13 and 18 as well as SCA. The types of fetal SCA and presence of ultrasound abnormalities are critical factors for the termination of pregnancy.
Aneuploidy ; Down Syndrome ; Female ; Fetus ; Humans ; Pregnancy ; Prenatal Diagnosis ; Sex Chromosome Aberrations ; Trisomy