[Chromosomal aberrations--the cause of spontaneous abortions]. / Aberracje chromosomowe jako przyczyna poronien samoistnych.

UNLABELLED: The genetic factor remains the most frequent cause of spontaneous abortions. Examination of the fetal tissue from spontaneous miscarriages shows that 75% of them were caused by abnormal karyotype. Other reasons, albeit rare, included submicroscopic genomic rearrangements, monogenic diseases, and polygenic inheritance disorders of the embryo. OBJECTIVE: The aim of the study was to analyze the incidence of chromosomal aberrations in material from the miscarriage. MATERIAL AND METHODS: The study included 47 samples of miscarriage material from 47 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination. RESULTS: Chromosomal abnormalities were diagnosed in 72% of the samples, with trisomy 21 (25.5%), trisomy 16 (17%), and trisomy 18 (12.8%) as the most common. An abnormal number of copies of chromosome 18, 21, 22, indicating the coexistence of trisomy 18, 21, 22, was detected in 1 patient. It was another miscarriage in case of 14 subjects (29.8%). CONCLUSIONS: Chromosomal aberrations were diagnosed in the majority of fetal tissue samples from spontaneous miscarriages. More than one chromosomal aberration in a single embryo is an extremely rare occurrence. Miscarriage due to chromosomal aberrations occurred in the vast majority of women > 35 years of age.

Triorchidism: genetic and imaging evaluation in an adult male.

We report the results of imaging and cytogenetic studies in a case of triorchidism in a 54 years old male without any associated anomaly. A scrotal ultrasonography revealed the presence of two testes within the left hemiscrotum with complete septation and echotexture and vascular flow pattern similar to the vascular flow of the normal right testis. There was no focal abnormal echogenicity suggesting malignancy. Scrotal MRI confirmed two soft-tissue structures in the left hemiscrotum with normal signal intensity at T1w and T2w images. Both testes had a tunica albuginea with low-signal intensity. Cytogenetic analysis resulted in normal male karyotype 46XY. Array-CGH analysis detected the presence of two interstitial rearrangements: a ~120 Kb deletion of chromosome 1 and a ~140 Kb deletion of chromosome 16. Currently there are little details on the functions of both genes.

Detection of a second t(14;18) breakpoint cluster region in human follicular lymphomas.

Our results indicate that there are two major breakpoint cluster regions in chromosome 18 DNA for t(14;18) translocations in follicular lymphomas. The absence of a pFL-1 homologous transcript in a cell line containing a pFL-2-detectable translocation suggests that there may be two different pathogenetic consequences of t(14;18) translocations. One possibility is that, despite the distances between them (greater than 20 kb), breakpoints in the two cluster regions in some way affect transcription of the same gene product, which has not yet been identified. Alternatively, two separate transcriptional units may be involved. The availability of DNA probes for each of the two t(14;18) breakpoint cluster regions will allow further studies regarding the biologic significance of these two genetically distinct classes of t(14;18) translocations.

LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells.

Lymphocyte function associated antigen 1 (LFA-1) is a leukocyte cell adhesion protein. We have studied a novel human immunodeficiency disease in which LFA-1 and two other proteins which share the same beta subunit are lacking from the surface of leukocytes. The basis of the inherited defect in cell surface expression of both the alpha and beta subunits of LFA-1 was determined by somatic cell fusion of patient or normal human cells with an LFA-1+ mouse T cell line. Human LFA-1 alpha and beta subunits from normal cells could associate with mouse LFA-1 subunits to form interspecies hybrid alpha beta complexes. Surface expression of the alpha but not the beta subunit of patient cells was rescued by the formation of interspecies complexes. The findings show that the LFA-1 alpha subunit in genetically deficient cells is competent for surface expression in the presence of an appropriate beta subunit, and suggest that the genetic lesion affects the beta subunit. The human LFA-1 alpha and beta subunits were mapped to chromosomes 16 and 21, respectively. The genetic defect is inferred to be on chromosome 21.

Eosinophilic differentiation of the human promyelocytic leukemia cell line, HL-60.

HL-60 promyelocytic leukemia cells differentiated to eosinophils and eosinophilic precursors when cultured under mildly alkaline conditions (pH 7.6-7.8) for 7 d without refeeding. New cytoplasmic granules appeared blue in the least mature cells and red in the most mature cells when stained with Wright-Giemsa. The granules also stained with Luxol-fast-blue, a characteristic of eosinophil granules. Furthermore, most cells contained the eosinophil major basic protein (MBP); the Charcot-Leyden Crystal (CLC) protein (lysophospholipase), eosinophil peroxidase, acid phosphatase, and arylsulfatase were also detected in a portion of these cells. The eosinophil major basic protein was found in a high proportion of undifferentiated cells, and thus may be constituitively produced. By examining finely banded chromosomes, translocation break points were demonstrated at q22 on one chromosome 16 and at q23 on the other homologue; abnormalities in this region of the long arm of 16 are a characteristic finding in the recently described syndrome of acute myelomonocytic leukemia (AMMoL) with abnormal bone marrow eosinophils. In common with the bone marrow eosinophils in these patients, the HL-60 eosinophil granules contained chloroacetate esterase and periodic-acid Schiff (PAS) reactive material; crystalloid inclusions were rare. Therefore, the HL-60 cell line appears to be an in vitro model for eosinophilopoiesis and may be specially suited for the study of the abnormal eosinophils seen in certain malignant conditions.

Prenatal diagnosis of craniomaxillofacial malformations: a characterization of phenotypes in trisomies 13, 18, and 21 by ultrasound and pathology.

OBJECTIVE: To determine the relationship between trisomies 13, 18, and 21 and craniofacial malformations detected by prenatal sonography. DESIGN: During a 29-year period (1976 through 2004), prenatal sonographic findings of 69 fetuses with trisomy 13; 171 fetuses with trisomy 18; 302 fetuses with trisomy 21; and 17 fetuses with other trisomies were evaluated retrospectively, after fetal karyotype identification. Sonographic findings were compared with autopsy results in 209 patients (trisomy 13, n=39; trisomy 18, n=64; and trisomy 21, n=106). RESULTS: For trisomy 13, cleft deformities were detected prenatally in 65.2%, and of the 39 cases with pathological information, 76.9% were found to have a cleft deformity. Ocular and orbital abnormalities were found in 28%. Malformations of the jaws and abnormal profiles were more frequently diagnosed postnatally than prenatally. For trisomy 18, abnormal profiles (41.5%) and ear abnormalities (5.3%) were the most noticeable ultrasound markers, next to abnormalities of the neurocranium (36.8%) and cranial bone configuration (21.6%). Dysmorphisms of the eye, ear, or nose were detected more frequently in autopsy cases. For trisomy 21, ultrasound showed an aberrant shape of the skull in 14.2% of fetuses. In general, the ocular-orbital and nasal abnormalities in fetuses with trisomy 18 or 21 were more evident in pathological examination than in prenatal ultrasound imaging. CONCLUSIONS: Facial anomalies are common in the major trisomies, and their prenatal sonographic identification should be improved. The above-mentioned facial anomalies provide sufficient reason to consider performing cytogenic evaluation.

[Frequency of chromosomal aberrations in material from abortions]. / Czestosc wystepowania aberracji chromosomowych w materiale z poronien.

UNLABELLED: Examination of fetal tissue from spontaneous miscarriages shows that 50-70% of them were caused by abnormal karyotype. The most frequent genetic abnormalities include abnormal number of chromosomes, aberration of chromosomes structure and chromosome mosaic anomalies. OBJECTIVE: The aim of the study was to find out whether there is any difference in the frequency of chromosomal aberrations in patients who miscarried for the first time comparing to patients with recurrent miscarriages. MATERIAL AND METHODS: Examination was performed on 129 miscarriage material samples from 128 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination. RESULTS: We received 120 results in which 45 (37,5%) were abnormal. The most frequent chromosomal aberration was trisomy followed by triploidy and monosomy of chromosome X. Among 59 samples from first miscarriage we found 25 abnormal karyotypes. In the 61 samples from the second, third and the next miscarriages we found 20 chromosomal abnormalities. CONCLUSIONS: Frequency of chromosomal aberrations in the tissue from the first miscarriage is significantly higher than in samples from second or following miscarriages, which means that genetic factors are less likely to induce recurrent miscarriages. Genetic results confirm that most chromosomal abnormalities arise de-novo.

[Do chromosomal abnormalities reappear in subsequent pregnancies and how often?]. / Czy i jak czesto aberracje chromosomowe zarodków powtarzaja sie w kolejnej ciazy?

OBJECTIVE: Genetic factors are the most common causes of spontaneous abortions. 50% to 80% of first-trimester abortions reveal-chromosome abnormalities. Evidence for the recurrence of the same or another chromosome abnormality in the next pregnancy is scarce. THE AIM: The aim of our study was to estimate recurrence risk of abortus aneuploidy and to find out whether karyotyping of the abortus allows the prognose subsequent pregnancy outcomes. MATERIAL AND METHODS: Paraffin-embedded chorions have undergone cytogenetic examination using FISH with chromosome-specific probes. 57 chorions from 26 women have been assessed, including chorions from two consecutive abortions from 18 women and chorions from three consecutive abortions from 5 women. RESULTS: 38.6% of 57 specimens had chromosome aberrations. The most prevalent anomalies were 16, 21 and 18 trisomies. 23 patients had a subsequent abortion karyotyped; 15 had a normal initial karyotype and 8 had an aberrant initial karyotype. 3 out of the 8 patients had a repeated chromosome anomaly 5 out of the 15 patients who initially miscarried an aneuploid embryo, had a subsequent miscarriage of an aneuploid embryo. Only 3 (13.04%) out of the 23 patients displayed aneuploidy in each abortus. CONCLUSION: (1) Chromosome aberrations can reappear in subsequent pregnancies in the same patient and may be the cause of recurrent miscarriages. (2) The value of embryo/fetal karyotyping is not decisive in prognosis of subsequent pregnancy outcome. (3) Abnormal fetal karyotype can occur regardless of other causes of pregnancy loss.

[Successful rituximab monotherapy in a patient with mucosa-associated lymphoid tissue lymphoma of the rectum with trisomy 3, 18].

A 62-year-old man was referred to our hospital with enlargement of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum after the eradication of Helicobacter pylori. The patient was given a diagnosis of stage I MALT. Endoscopic observation revealed an enlarged rectal tumor with 3, 18 double trisomy. Rituximab monotherapy was given and complete remission was achieved. Rituximab monotherapy can be useful for MALT lymphoma of the rectum.

Multigene family for sarcomeric myosin heavy chain in mouse and human DNA: localization on a single chromosome.

Cloned myosin heavy chain DNA probes from rat and human were hybridized to restriction endonuclease digests of genomic DNA from somatic cell hybrids and their parental cells. The mouse myosin heavy chain genes detectable by this assay were located on chromosome 11, and three different human sarcomeric myosin heavy chain genes were mapped to the short arm of chromosome 17. A synteny between myosin heavy chain and two unrelated markers, thymidine kinase and galactokinase, was found to be preserved in the rodent and human genomes.

Involvement of the bcl-2 gene in human follicular lymphoma.

Recombinant DNA probes were cloned for the areas flanking the breakpoint on chromosome 18 in cells from a patient with acute lymphocytic leukemia of the B-cell type; cells of this line carry the t(14;18) chromosomal translocation. Two of the probes detected DNA rearrangements in approximately 60 percent of the cases of follicular lymphoma screened. In follicular lymphoma, most of the breakpoints in band q21 of chromosome 18 were clustered within a short stretch of DNA, approximately 2.1 kilobases in length. Chromosome 18-specific DNA probes for the areas flanking the breakpoints also detected RNA transcripts 6 kilobases in length in various cell types. The gene coding for these transcript (the bcl-2 gene) seems to be interrupted in most cases of follicular lymphomas carrying the t(14;18) chromosomal translocation.

Human thymidine kinase gene locus: assignment to chromosome 17 in a hybrid of man and mouse cells.

The human chromosome retained in a hybrid clone derived from human cells and a moluse line deficiemt in thymidine kinase has the quinacrinefluorescence pattern characteristic of chromosome 17.

Polymorphism of human constitutive heterochromatin.

Genetic polymorphism has been demonstrated in man for many characteristics including blood groups, serum proteins, tissue enzymes, and hemoglobins. A class of chromosomal polymorphism involving constitutive heterochromatin has now been found. Through the use of a special technique that permits visualization of heterochromatin, seven heterochromatin variants have been found among four individuals. These results suggest a very high frequency of variability of heterochromatin in the population.

Identification of the constant chromosome regions involved in human hematologic malignant disease.

Specific consistent chromosome translocations are regularly observed in certain human leukemias and lymphomas. For the myeloid leukemias, the constant recombinants are: the long arm of 9 to chromosome 22 in chronic myeloid leukemia, the long arm of 21 to chromosome 8 in acute myeloblastic leukemia, and the long arm of 17 to chromosome 15 in acute promyelocytic leukemia. Three related translocations are seen in Burkitt lymphoma and B cell acute lymphocytic leukemia; in each one, chromosome 8 is involved with chromosome 2, 14, or 22. Analysis of a complex translocation affecting chromosomes 8 and 14 indicates that the translocation of chromosome 8 to chromosome 14 is the critical constant rearrangement. The analysis of the DNA at the translocation sites of these chromosomes, rather than the reciprocal of each translocation, appears to be the most productive focus for initial study. The various immunoglobulin loci are located in chromosomes 2, 14, and 22, the chromosomes regularly involved in translocations in Burkitt lymphoma and B cell acute lymphocytic leukemia.

Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways.

A new family of protein kinase C-related genes has been identified in bovine, human, and rat genomes. The alpha-, beta-, and gamma-type protein kinase sequences are highly homologous, include a kinase domain, and potential calcium-binding sites, and they contain interspersed variable regions. The corresponding genes are located on distinct human chromosomes; the possibility of even greater genetic complexity of this gene family is suggested by Northern and Southern hybridization analyses.

Heritable fragile site on chromosome 16: probable localization of haptoglobin locus in man.

We have found recurrent chromosome breaks at a site (the "fragile site") on the long arm of chromosome 16. This site segregates in simple Mendelian dominant fashion in a large family. The distal portion of the chromosome sometimes shows selective endoreduplication. Preliminary linkage results reveal only 3 recombinants in 33 opportunities for recombination between the fragile site and the alpha locus of haptoglobin, an indication that the alpha-Hp gene is located near this region on chromosome 16.

Location of the c-yes gene on the human chromosome and its expression in various tissues.

Analysis of DNA from human embryo fibroblasts showed that ten Eco RI fragments were hybridizable with the Yamaguchi sarcoma virus oncogene (v-yes). Four of the Eco RI fragments were assigned to chromosome 18 and one to chromosome 6. There was evidence for multiple copies of yes-related genes in the human genome; however, only a single RNA species, 4.8 kilobases in length, was related to yes in various cells.

Chromosomal location of human metallothionein genes: implications for Menkes' disease.

Human metallothioneins are encoded by a complex multigene family. The chromosomal location of these genes has been determined by gel transfer hybridization analysis of the DNA from human-rodent cell hybrids. Chromosome 16 contains a cluster of metallothionein sequences, including two functional metallothionein I genes and a functional metallothionein II gene. The remaining sequences, including a processed pseudogene, are dispersed to at least four other autosomes. The absence of metallothionein sequences from the X chromosome indicates that Menkes' disease, an X-linked disorder of copper metabolism, affects metallothionein expression by a trans-acting mechanism.

Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans.

The human genes for growth hormone (GH), chorionic somatomammotropin (CSH), and a third growth hormone-like gene (GHL) have been located on chromosome 17 in humans. DNA fragments of 2.6, 2.8, and 9.5 kilobase pairs containing GH, CSH, and GHL, respectively, were identified in human genomic DNA, and a 7.5-kilobase DNA fragment related to growth hormone DNA sequences was found in mouse cells. In somatic hybrids of human and mouse cells containing reduced numbers of human chromosomes, but a normal complement of mouse chromosomes, the mouse, 7.5-kolobase DNA fragment was always present, whereas the 2.6-, 2.8-, and 9.5-kilobase human fragments were present only when human chromosome 17 was also present.

Assignment of the murine interferon sensitivity and cytoplasmic superoxide dismutase genes to chromosome 16.

Both hybrids of mouse and human microcells and whole cell hybrids generated by the fusion of primary mouse cells and SV40-transformed human fibroblasts were used to establish the syntenic association of the murine cytoplasmic superoxide dismutase and the interferon sensitivity genes on mouse chromosome 16. This assignment adds two new markers to chromosome 16 and provides another example of an evolutionarily conserved linkage. This finding also provides an animal model both for cellular responsiveness to interferon and for Down's syndrome.