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

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

OBJECTIVE: To assess the value of chromosomal karyotyping analysis and single nucleotide polymorphism-based microarray (SNP-array) for the detection of chromosomal mosaicisms in amniotic fluid samples. METHODS: Seventy four pregnant women with fetal mosaicisms detected by both methods were retrospectively analyzed. RESULTS: Among the 74 mosaicisms, 12 were pseudo and 62 were true mosaicisms, which included 1 Robertsonian translocation, 3 deletions, 4 supernumerary markers, 19 autosomal aneuploidy mosaicisms, 30 sex chromosome aneuploidy mosaicisms and 5 isometric chromosome mosaicisms. CONCLUSION Chromosome karyotyping analysis and SNP-array have their own advantages and limitations for the diagnosis of mosaicisms. When the two methods have yielded inconsistent results, fluorescence in situ hybridization may be used for further verification.
Aneuploidy ; Chromosome Aberrations ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Mosaicism ; Pregnancy ; Prenatal Diagnosis/methods* ; Retrospective Studies ; Sex Chromosome Aberrations

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

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: Genetic defects of the zygote, such as chromosome aberration, are the most frequent cause of abnormal embryonic development and spontaneous abortion. Recent advances in ultrasonographic technology have allowed documentation of early embryonic growth and development and some studies have suggested that once fetal cardiac activity has been demonstrated at 8-10 weeks of gestation, the subsequent spontaneous abortion rate is reported to be less than 5% of pregnancies. Some authors suggested that, abortions in which fetal cardiac activity was once demonstrated, chromosomal anomalies are considered to play important roles in these abortions. But, other studies failed to reveal any relationship between occurrence of chromosomal abnormalities and ultrasonographic detection of fetal heart activity. The aim of the study was to determine the relationship of ultrasonographic detection of fetal heart activity and the abnormal karyotypes in spontaneous abortions. DESIGN: A 1-year retrospective, study. MATERIALS AND METHODS: 158 pregnancies (129 spontaneous, 29 assisted ovulatory cycles) that aborted in the first trimester between January 1,2001 and December 31, 2001, in Samsung Cheil Hospital had chromosomal analysis performed on the products of conception and had ultrasonographic examination prior to spontaneous abortion. Of these pregnancies 62 were detection of transvaginal ultrasonographic detection of fetal heart activity prior to abortion and 96 were failure to detect fetal heart activity. Fetal tissue was removed by dilatation and curettage. Cytogenetic studies were performed from cultures of dissected chorionic villi and G-sac. And then, we compared the incidence and the characteristics of abnormal karyotypes between fetal heart activity detected group (Group I) and failure to detect fetal heart activity group (Group II) prior to abortion. RESULTS: Of 158 spontaneous abortions who carrying chromosomal analysis, 98 had abnormal karyotypes. (60 trisomies, 11 polyploides, 10 mosaicism, 5 monosomies and 12 structural abnormalities). The overall incidence of chromosomal aberrations in our study group was 62.0% (98/158). Chromosomal aberrations were found in 59.7% (37/62) of abortuses in group I and 63.5% (61/96) in group II and it was insignificant statistically. The frequency of type of abnormal karyotype in both groups (Group I: 25 (40.3%) trisomies, 1 (1.6%) polyploides, 0 (0%) mosaicism, 8 (12.9%) and 3 (4.8%) monosomies, Group II: 35 (36.5%) trisomies, 10 (10.4%) polyploides, 5 (5.2%) mosaicism, 2 (2.1%) monosomies and 9 (9.4%) structural abnormalities) were insignificant statistically. When we stratified both groups and analyzed the abnormal karyotype by maternal age, those were not statistically different in both groups. CONCLUSION: In our study, chromosomal abnormalities in spontaneous abortion did not differ according to ultrasonographic detection of fetal heart activity, and the type of abnormal karyotype were not distributed differently.
Abnormal Karyotype ; Abortion, Spontaneous ; Chorionic Villi ; Chromosome Aberrations ; Cytogenetics ; Dilatation and Curettage ; Embryonic Development ; Female ; Fertilization ; Fetal Heart* ; Fetus ; Growth and Development ; Humans ; Incidence ; Karyotype* ; Maternal Age ; Monosomy ; Mosaicism ; Polyploidy ; Pregnancy ; Pregnancy Trimester, First* ; Retrospective Studies ; Trisomy ; Zygote

Holoprosencephaly of unknown definite causes, has been associated with several chromosome abnormalities involving the autosomes and the sex chromosomes. The most commonly reported associations include dup(3p), del(7q), deletions of chromosome 13, trisomy 13, trisomy 18, and triploidy. In previously reported cases in Korea, none were associated with chromosome 21 anomalies. In conclusion, we reported the first case of holoprosencephaly(semilobar type) associated with pure monosomy 21. We experienced a semilobar type holoprosencephaly with monosomy 21 in a neonate who had multiple congenital anomalies, including an abnormal face, a small thorax with widely spaced hypoplastic nipples and nail hypoplasia, lung hypoplasia with severe scoliosis and cardiac abnormalities. Chromosomal analysis revealed a 45, XY, -21.
Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 21 ; Holoprosencephaly ; Humans ; Infant, Newborn ; Korea ; Lung ; Monosomy ; Nipples ; Scoliosis ; Sex Chromosomes ; Thorax ; Triploidy ; Trisomy

Noninvasive prenatal test (NIPT) is a novel screening method for the diagnosis of fetal chromosomal aneuploidies. NIPT is based on technology that detects cell-free fetal DNA in maternal plasma and analyzes it with massively parallel sequencing technology to determine whether the fetus is at risk of trisomy 21, trisomy 18, trisomy 13 or sex chromosome abnormalities (SCAs). NIPT has been reported to have sensitivity of 99% and a false positive rate of less than 1% for detecting trisomy 21 and trisomy 18. Although extension of the application of NIPT to other SCAs has been attempted, there are concerns in extending NIPT to SCAs because of maternal or fetal mosaicism, undetected maternal SCAs, and multiple pregnancies. Recently, we assessed a pregnancy with the rare Turner syndrome mosaicism 45, X/47, XXX, which was reported as 45, X with NIPT. We present the case here and briefly review the current literatures on NIPT in testing for fetal monosomy X. To the best of our knowledge, this is the first report of the 45, X/47, XXX mosaicism in Korea to be reported as 45, X by NIPT with whole genome sequencing. This case report will provide valuable information for counseling women who want to undergo NIPT.
Aneuploidy ; Counseling ; Diagnosis ; DNA ; Down Syndrome ; Female ; Fetus ; Genome ; High-Throughput Nucleotide Sequencing ; Humans ; Korea ; Mass Screening ; Mosaicism* ; Plasma ; Pregnancy* ; Pregnancy, Multiple ; Prenatal Diagnosis ; Sex Chromosome Aberrations ; Trisomy ; Turner Syndrome*

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

OBJECTIVE: To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. METHODS: A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. RESULTS: The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05). CONCLUSION No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.
Humans ; Mosaicism ; In Situ Hybridization, Fluorescence/methods* ; Retrospective Studies ; Karyotyping ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Karyotype ; Chromosome Banding ; Sex Chromosomes