Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O75695 (X-linked recessive)
 2,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new X-linked recessive lymphoproliferative syndrome has variable phenotypes: fatal infectious mononucleosis (I.M.), agammaglobulinaemia after I.M., American Burkitt's lymphoma, histiocytic lymphoma, immunoblastic sarcoma of B cells, or plasmacytoma. An immunodeficiency to rubeola and the Epstein-Barr virus probably ensues from the mutant gene. The phenotypes (spectrum of B-cell disorders) have a common inheritance and the aetiology is similar.
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PMID:Pathogenesis and phenotypes of an X-linked recessive lymphoproliferative syndrome. 6 16

Investigation of a family with cancer in boys revealed that at least 20 males had the X-linked recessive lymphoproliferative syndrome. A variety of phenotypes occurred: aproliferative phenotypes consisted of aplastic anemia, agranulocytosis or acquired hypogammaglobulinemia; and proliferative phenotypes of B cells included disorders associated with the Epstein-Barr virus, American Burkitt's lymphoma, immunoblastic sarcoma of B cells, fatal infectious mononucleosis or plasmacytoma. The lymphoproliferative disorders observed in males could have resulted from an immunodeficiency to Epstein-Barr virus. The variable phenotypic expression could have resulted from individual differences in the viral dose, duration of exposure and age at which the boys were exposed to the virus. Aproliferative phenotypes such as acquired hypogammaglobulinemia could have ensued from excessive suppressor-cell activity on B cells, whereas proliferative phenotypes such as Burkitt's lymphoma or fatal infectious mononucleosis could have resulted from infection by Epstein-Barr virus and failure to stop proliferation of B cells.
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PMID:Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. 19 60

Subtle immunodeficiency to infectious agents including measles virus and ten Epstein-Barr virus (EBV) has been described in the X-linked recessive lymphoproliferative syndrome. This syndrome has affected six male cousins and possibly another boy. Three brothers died of an infectious mononucleosis syndrome, in a maternal cousin agammaglobulinemia developed three years after infectious mononucleosis, and two half-brothers of the Duncan kindred died of lymphoma of the brain and intestinal tract, respectively. In three of the boys, unusual measles viral infections had developed. Paramyxovirus-like particles suggestive of measles virus were seen at necropsy in the atrophic lymphoid tissue of two boys. Also, numerous plasma cells were seen in the brains, visceral organs and the thymus glands, and thymic-dependent lymphocytes were sparse in lymph nodes and spleen. The abnormal lymphopoiesis in the syndrome probably results from a subtle immunodeficiency, and concurrent measles and EB virus infections.
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PMID:Hematopathology and Pathogenesis of the X-linked recessive lymphoproliferative syndrome. 83 2

The Wiskott-Aldrich syndrome is an uncommon X-linked recessive disease characterized by eczema, thrombocytopenia, and immunodeficiency. The clinical features begin early in life and include recurrent infections, bleeding, and severe eczema. Unless the condition is treated by bone marrow transplantation, the prognosis of Wiskott-Aldrich syndrome is grave, and premature death caused by sepsis, hemorrhage, or lymphoreticular malignancy is common. Although the biochemical defect responsible for the syndrome is not known, recent investigations with restriction fragment length polymorphisms have mapped the Wiskott-Aldrich syndrome locus to the proximal portion of the short arm of the human X chromosome (Xp11). The isolation of these DNA markers makes feasible both carrier detection and prenatal diagnosis of Wiskott-Aldrich syndrome and provides an important adjunct to the management of Wiskott-Aldrich syndrome for patients and their families. These genetic data, in conjunction with the recent identification of a specific O-glycosylation defect in lymphocytes from patients with Wiskott-Aldrich syndrome, present an opportunity for the eventual isolation of the Wiskott-Aldrich syndrome gene and identification of the underlying cellular defect. We review the clinical and laboratory features of this syndrome and summarize the new molecular and biochemical approaches that can be used in diagnosis, genetic counseling, and treatment.
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PMID:Wiskott-Aldrich syndrome: new molecular and biochemical insights. 140 1

The Wiskott-Aldrich syndrome (IMD2) is an X-linked recessive immunodeficiency. Initial linkage studies mapped the disease locus on the proximal short arm of the X chromosome, a localization which was further refined to the interval framed by DXS7 and DXS14. We have recently shown that a novel hypervariable locus, DXS255, is very closely linked to the disease gene and is likely to be, at present, the marker closest to the disease gene. The analysis of one family, however, displayed conflicting linkage results, as all of the informative markers situated in the Xp11-q22 region appeared to recombine with the disease locus in two "phase-known" meioses. We have shown by X-inactivation studies that the segregation of the disease through three obligate carrier females in this family originates from a grandpaternal mosaicism, which accounts for the apparent recombinations. This shows that germ-line mosaicism can simulate genetic heterogeneity in linkage studies.
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PMID:Germ-line mosaicism simulates genetic heterogeneity in Wiskott-Aldrich syndrome. 197 Nov 43

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immunodeficiency affecting B lymphocytes, T lymphocytes, and platelets. Previous studies on lymphocytes from WAS patients have revealed that leu-kosialin (CD43), a cell-surface glycoprotein bearing approximately 90 O-linked oligosaccharide chains, shows an aberrant electrophoretic mobility. To determine whether this finding reflects a different pattern of O-linked glycosylation in WAS cells, we have compared healthy individuals and WAS patients with respect to glycosyltransferase activities in T lymphocytes, platelets, and Epstein-Barr virus (EBV)-immortalized B cell lines. Stimulation of peripheral T cells from normal individuals in vitro with anti-CD3 antibodies and interleukin-2 was associated with a 3-fold increase in UDP-GlcNAc:Gal beta 3GalNAc-R (GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (core 2 GlcNAc-T) from 0.8 to 2.2 nmol/mg/h. In contrast, peripheral T lymphocytes from WAS patients showed an inversion of this phenotype with high core 2 GlcNAc-T activity in unstimulated cells (2.3 nmol/mg/h) and a 2-3-fold decrease in activity following stimulation. Core 2 GlcNAc-T activity was also three times higher in platelets from WAS patients than in normal platelets. Glycosyltransferase activities were measured in immortalized B cell lines established from WAS and normal subjects by infection with EBV. Core 2 GlcNAc-T was less than 0.4 nmol/mg/h in WAS EBV-B cell lines compared to 2.4 nmol/mg/h in EBV-B cell lines from healthy individuals, In contrast, CMP-SA:SA alpha 2-3Gal beta 1-3GalNAc-R (where SA represents sialyl (sialic acid to GalNAc) alpha 6-sialyltransferase II activity was 2.0 nmol/mg/h in the WAS EBV-B cell and less than .01 nmol/mg/h in EBV-B cell lines derived from normal subjects. Eleven other glycosyltransferase activities were measured and found to be similar in EBV-B cell lines from WAS and normal individuals. Polylactosamine sequences were much reduced in the O-linked oligosaccharides of CD43 from WAS EBV-B cells consistent with decreased core 2 GlcNAc-T activity and expression of core 1 oligosaccharides in the cells. In conclusion, B cells, T cells, and platelets in WAS patients show abnormal expression of two developmentally regulated glycosyltransferases, consistent with the idea that the WAS immunodeficiency is due to a failure of normal lymphocyte maturation.
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PMID:Aberrant O-linked oligosaccharide biosynthesis in lymphocytes and platelets from patients with the Wiskott-Aldrich syndrome. 200 80

Humoral (or antibody) immunodeficiency syndromes may occur as apparent congenital or acquired abnormalities, with deficiencies in all or in only some classes of immunoglobulins. Most patients are recognized because of recurrent infections with high-grade extracellular encapsulated bacterial pathogens, but some with selective IgA deficiency or with transient hypogammaglobulinemia of infancy may have few or no infections. Although general population statistics are not available, most defects are thought to be rare; humoral immunodeficiency is more prevalent than cellular immunodeficiency, possibly due to early death from the latter defects. Disorders affecting B-cell function may be inherited as X-linked recessive or as autosomal traits. Although considerable information exists about such defects at a functional and cellular level, the primary biologic errors are as yet unknown for all of them. Apparent abnormalities of B-cell maturation and/or intrinsic B-cell malfunction are seen in a majority of these defects. The heterogeneity of B-cell morphology and function in large pedigrees of patients with X-linked agammaglobulinemia makes it unlikely that the defect is due to a distinct gene rearrangement abnormality at a specific stage of B-cell maturation. Early recognition of B-cell deficiency and institution of adequate immunoglobulin replacement therapy can prevent extensive damage to the lungs and other life-threatening problems from infection and allow a relatively normal childhood and adult life.
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PMID:Humoral immunodeficiency. 242 51

Eleven families segregating for the X-linked recessive immune deficiency disorder, Wiskott-Aldrich syndrome (WAS), were studied by linkage analysis with an alpha satellite DNA probe, pBamX-7, which detects polymorphisms at the X chromosome centromere, locus DXZ1, as well as three other polymorphic markers defining loci on the proximal short arm of the X chromosome. Linkage has been established between WAS and DXZ1 (zeta (theta) = 7.08 at theta = 0.03) and WAS and the TIMP gene locus (zeta (theta) = 5.09 at theta = 0.0). We have also confirmed close linkage between DXZ1 and two marker loci, DXS14 and DXS7, previously shown to be linked to the WAS locus. The probe pBamX-7 detected allelic variation in all females tested, reflecting the high frequency of polymorphism at the centromere. One WAS carrier revealed a recombination between WAS and both marker loci DXZ1 and DXS14, indicating that WAS does not map between these loci. In conjunction with previous data from genetic mapping studies of WAS, these results confirm the pericentromeric Xp localization of WAS and demonstrate the usefulness of alpha satellite DNA probes as tools for genetic prediction in WAS as well as other pericentric X-linked diseases.
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PMID:Linkage studies of the Wiskott-Aldrich syndrome: polymorphisms at TIMP and the X chromosome centromere are informative markers for genetic prediction. 257 60

The authors report a case of a 20-year old woman, with all the characteristics of the Wiskott-Aldrich-syndrome. The main signs of the disease were recurrent infections, eczema, thrombocytopenia and mild mucosal bleeding. The size of platelets was reduced. Storage pool disease was based on the abnormal platelet aggregation and the lack of dense bodies shown by electronmicroscopic examination. The disturbances of the lymphocytes, neutrophils and monocytes, which resulted in immunodeficiency, could be proven by the immunological tests. This X-linked recessive disorder appeared with typical signs in a heterozygous carrier woman. According to our knowledge, no similar case has been reported before.
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PMID:[Wiskott-Aldrich syndrome in a hetrozygous woman]. 265 54

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease characterized by immunodeficiency and severe thrombocytopenia in affected males, but no demonstrable clinical abnormalities in carrier females. Through analysis of the methylation patterns of X-linked genes that display restriction fragment length polymorphisms (RFLPs), we studied the pattern of X-chromosome inactivation in various cell populations from female relatives of patients with WAS. The peripheral blood T cells, granulocytes, and B cells of eight obligate WAS carriers were found to display specific patterns of X-chromosome inactivation clearly different from these of normal controls. Thus, carriers of WAS could be accurately identified using this analysis.
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PMID:Carrier detection in the Wiskott Aldrich syndrome. 326 54


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