1/27. Pure red cell aplasia in a patient with trisomy x chromosome abnormality and reactivated Epstein-Barr virus infection.We describe a woman with a congenital chromosome anomaly, 47,XXX, who developed chronic pure red cell aplasia (PRCA). The patient had serologic reactivity consistent with that of reactivated Epstein-Barr virus (EBV) infection, as judged by high titers for anti-EBV viral capsid antigen (VCA) immunoglobulin g (IgG) and anti-early antigen (EA) IgG. Detection of EBV genome in peripheral blood cells and cell-free serum also supported the diagnosis. Although EBV infection has been implicated in the pathogenesis of acute PRCA, the viral infection rarely results in a chronic disease state. So far, only 1 case of EBV-associated chronic PRCA has been reported, to the best of our knowledge. Chronic PRCA also is known to occur on an autoimmune basis. Individuals carrying an extra x chromosome, such as XXY and XXX, are prone to development of immune abnormalities. Our patient had an anti-dna autoantibody and a positive result of the direct coombs test. The pathogenesis of PRCA in this case seemed to involve multiple factors. In addition to the infectious agent, host factors may have played a role. Although the etiologic link between chronic PRCA and trisomy X remains to be elucidated, our findings suggest the importance of karyotype analysis as well as search for infectious agents in patients with chronic PRCA.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/27. Two malignant peripheral primitive neuroepithelial tumor cell lines established from consecutive samples of one patient: characterization and cytogenetic analysis.A 6-year-old girl presented with a tumor of the right shoulder involving bone, adjacent soft tissue, and regional lymph nodes. The conventional histologic diagnosis was ambiguous, initially suggesting lymphoma. After relapse on lymphoma therapy, reevaluation with additional multiple diagnostic techniques performed on the biopsy tissue and on two cell lines derived from the biopsies established the diagnosis of a primitive neuroepithelial tumor of bone and soft tissue. This was strongly supported by 1) focal rosette formation by the tumor cells and positive immunostaining for neuron-specific enolase and synaptophysin, with absent staining for leukocyte common antigen; 2) at the ultrastructural level, formation of cellular processes containing microtubules, a paucity of neurosecretory granules, absence of synaptic junctions, formation of long "intermediate" junctions between cells, and, in culture, widespread development of rosettes; 3) marked surface positivity to W 6/32 and negativity to HSAN 1.2 antibodies; and 4) elevated expression of MYC and lack of overexpression of MYCN oncogenes. Numerical and structural abnormalities were present in the karyotype, but the expected t(11;22)(q24;q12) was not present in the tumor-involved marrow or in either of the established tumor cell lines, although there was an interstitial deletion of 11q involving breakpoints in q21 and q23.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
3/27. Flow cytometric diagnosis of X-linked hyper-IgM syndrome: application of an accurate and convenient procedure.Hyper-IgM (HIM) syndrome encompasses a family of congenital immunodeficiency states characterized by frequent infections and markedly low serum levels of IgG, IgA, and IgE but normal or elevated levels of IgM. Many patients have neutropenia. The major defect shared by all forms of HIM syndrome is a failure of immunoglobulin isotype-switching. Recently, a flow cytometric assay was described in the immunology literature for diagnosis of patients with inherited X-linked (X-HIM) syndrome. Using this assay, activated CD4 peripheral blood T lymphocytes from two patients suspected of having HIM syndrome, and from their mothers, were subjected to immunofluorescent flow cytometric analysis for the expression of cd40 ligand (CD154 antigen). Test results established the diagnosis of X-HIM syndrome that was inherited in one patient and spontaneous in the other. The authors' experience illustrates that the flow cytometric assay used and described in detail here can facilitate an accurate and timely diagnosis of X-HIM syndrome. Because the assay can be carried out in most clinical flow cytometry facilities, it lends itself to use by pediatric hematologists in the standard evaluation of patients whose differential diagnosis includes that disorder. The authors hope this report will raise awareness of the value of this procedure.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
4/27. Genotyping of AR and PSA polymorphisms in a patient with klinefelter syndrome, non-Hodgkin lymphoma, and adenocarcinoma of the prostate.It has been hypothesized that the AR (androgen receptor) gene binds the two PSA (prostate-specific antigen) alleles with differing affinities and may differentially influence prostate cancer risk. In this article, we report a case of adenocarcinoma of the prostate in a 56-year-old man with klinefelter syndrome (47,XXY) and non-Hodgkin lymphoma, as well as the AR and PSA genotype. AR and PSA gene polymorphisms were analyzed by polymerase chain reaction-based methods using dna from peripheral white blood cells and the prostate cancer. We determined the methylation status of the AR gene on the x chromosome. The patient presents with the AG genotype for the ARE-1 (androgen response element) region of the PSA gene. We detect the presence of two short AR alleles with 19 and 11 CAG repeats each. Unmethylated alleles were demonstrated for both. The shorter allele was inactive in more than 60% of total dna in both control blood and prostate cancer cells. The presence of short AR alleles and the G allele of the PSA gene may contribute to the development of prostate cancer in a 47,XXY patient.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
5/27. Sex reversal syndrome (XX male).men who appear normal and live a normal life, may have a 46,XX karyotype and present with the typical features of infertility and end organ (testicular) failure. They are azoospermic and their small testicles show specific patterns on light and electron microscopy. Recent advances in genetics (1) favor the "X-Y interchange" theory to explain this phenomenon; (2) hypothesize about the roles of the h-y antigen and testis determining factor (TDF) in determining "maleness"; and (3) allow mapping of the relative positions of H-Y and TDF loci on the y chromosome.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
6/27. fetal blood sampling demonstrating chimerism in monozygotic twins discordant for sex and tissue karyotype (46,XY and 45,X)fetal blood sampling has been used in the genetic work-up of twin gestations for rapid karyotyping. We present a case of twins which on ultrasound evaluation revealed hydrops fetalis in one twin and a normal second twin. fetal blood sampling revealed the presence of mosaicism for 46,XY/45,X in both twins. HLA antigen testing showed the twins to be identical. The patient elected pregnancy termination. Blood chromosomal analysis after delivery revealed both twins to have 46,XY/45,X mosaicism, but the twin with signs of hydrops fetalis had tissue chromosomes of 45,X and the normal twin had tissue chromosomes of 46,XY. amniotic fluid chromosomal analysis revealed 46,XY in twin A and 45,X in twin B. This represents a case of identical (monozygotic) twins with sex discordance. In this case, there was the probable occurrence of post-zygotic chromosomal non-disjunction leading to the discordancy of the sex in this set of twins. With the presence of vascular communication in monozygotic twins, there is the possibility of exchange of blood in monozygotic twins and the result of blood chimerism in twins.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
7/27. female haemophilia A in a family with seeming extreme bidirectional lyonization tendency: abnormal premature X-chromosome inactivation?We studied a female child with mild classical haemophilia A, presenting with a F VIII deficiency similar to that detected in her maternal grandfather. Investigations on several occasions showed that the obligate carrier mother of the proposita had normal VIII:C activity, whereas her likewise obligate carrier sister had a typical carrier VIII:C/vWf:Ag pattern. The child was a phenotypically normal female with normal karyotype. Her father had no clinical or biochemical signs of haemophilia A. RFLP-analysis using DX13 and St14 probes each elicited one allele (5.8 and 3.4 kb, respectively) segregating along with the affected F VIII gene from the hemizygous grandfather to both his daughters and further to the haemophilic female child. The paternity of the child was analyzed using various red cell and hla antigens and RFLP by p29C, a probe detecting polymorphic hypervariable TaqI and PstI fragments in the pseudoautosomal areas of the X- and Y-chromosomes. All results obtained were concordant with the declared paternity. RFLP-analysis, using single (Pst I) and double digestion (Pst I/Hha I) of dna and a PGK probe, revealed a remarkable difference in hybridization fragments, strongly suggesting hypermethylation, and in consequence, preferential X-chromosome inactivation in the proposita. This points to extreme lyonization as the most plausible explanation for haemophilia A in this female child. A familial tendency to abnormal premature X-chromosome inactivation is speculated.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
8/27. Duchenne muscular dystrophy in monozygotic twins: deletion of 5' fragments of the gene.A recombinant dna study for deletion evaluation was performed in a 4 generation family with Duchenne muscular dystrophy (DMD) in twins. The patients were 6 years old, had a history of progressive difficulty in walking since age 4, and showed weak gluteals, iliopsoas, latissimus dorsi, rhomboids, lower trapezius, sternocleidomastoids, pseudohypertrophic calves, and tight heelcords. Both patients had high serum creatine kinase of 19,000 and 11,000 IU, respectively, and the muscle biopsy of the left vastus lateralis showed dystrophic alterations. Both twins had the same red cell types for ABO, Rh, CDE, MNSs, Kelly, Lewis, Duffy, and Kidd. HLA typing also detected the same antigens in both twins: A2, B44, DR4, and DR5. Cytogenetic studies were consistent with 46, XY male individuals with normal banding pattern. By cDNA probes the entire DMD gene was surveyed for missing or abnormal-sized restriction fragments. Both twin boys showed absence of 8.5, 8.0, 4.6, 4.2, and 3.1 kb fragments on Hind III blots and absence of 13.5, 3.7, 2.9, and 1.4 kb fragments on Bgl II blots both hybridized with cDNA 1-2a corresponding to most 5' region of the DMD gene. The mother and other relatives of the patient did not show deletion. These findings strongly suggest that the deletion in the DMD monozygotic twins represents a new mutation.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
9/27. A theory explaining the abnormality in 45,X/46,XY mosaicism with non-fluorescent y chromosome. presentation of three cases.Three patients with male habitus, short stature and testicular differentiation are described. All had mos 45,X/46,XY, the ratio of the two stemlines varying between the patients and between different tissues. The y chromosome was abnormal, lacking the brilliant QFQ fluorescence and dark CGB staining characteristic of the distal part of the normal Y. Detailed banding studies suggested that the short arm and proximal part of the long arm were normal, while the distal part of the long arm was molecularly or otherwise altered, resulting in abnormal staining properties. Two of the patients were tested for h-y antigen and found to be positive. These data and those collected from the literature are compatible with a model in which the primary lesion in X/XY mosaicism is a molecular alteration in the reiterated Y-specific dna sequences (and possibly neighbouring sequences) of a 46,XY zygote resulting in the frequent mitotic loss of the Y and the emergence of a 45,X line. Provided the testis-determining gene(s) near the centromere are normal, testes are formed and the patient is H-Y antigen-positive. The extent of male or female differentiation depends in part on the prevalence, time of occurence, and distribution of the 45,X line and possibly in part on the alteration of other genes involved in sex differentiation and located on Yq further from the centromere.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/27. Localization of the McLeod locus (XK) within Xp21 by deletion analysis.The McLeod phenotype is an X-linked, recessive disorder in which the red blood cells demonstrate acanthocytic morphology and weakened antigenicity in the Kell blood group system. The phenotype is associated with a reduction of in vivo red cell survival, but the permanent hemolytic state is usually compensated by erythropoietic hyperplasia. The McLeod phenotype is accompanied by either a subclinical myopathy and elevated creatine kinase (CK) or X-linked chronic granulomatous disease (CGD). Seven males with the McLeod red-blood-cell phenotype and associated myopathy but not CGD, one male with the McLeod phenotype associated with CGD, and two males known to possess large deletions of the Duchenne muscular dystrophy (DMD) locus were studied. dna isolated from each patient was screened for the presence or absence of various cloned sequences located in the Xp21 region of the human x chromosome. Two of the seven males who have only the McLeod phenotype and are cousins exhibit deletions for four Xp21 cloned fragments but are not deleted for any portion of either the CGD or the DMD loci. Comparison of the cloned segments absent from these two McLeod cousins with those absent from the two DMD boys and the CGD/McLeod patient leads to the submapping of various cloned dna segments within the Xp21 region. The results place the locus for the McLeod phenotype within a 500-kb interval distal from the CGD locus toward the DMD locus.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
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