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Aldrich Syndrome (aldrich + syndrome)

Distribution by Scientific Domains

Medical Sciences	76%
Life Sciences	23%

Selected Abstracts

Early transplantation of unrelated cord blood in a two-month-old infant with Wiskott,Aldrich syndrome

PEDIATRIC TRANSPLANTATION, Issue 5 2007
Tang-Her Jaing
Abstract:, This report exemplified a success of unrelated CBT in a two-month-old boy with Wiskott,Aldrich Syndrome. Umbilical cord blood was chosen as the stem-cell source because of its immediate availability and reduced tendency to cause GVHD. The conditioning regimen was cyclophosphamide, busulfan, and antithymocyte globulin. GVHD prophylaxis consisted of cyclosporin and methylprednisolone. The patient received an HLA 1-locus-mismatched cord blood unit, and the total number of infused nucleated cells was 11.14 × 107/kg. Neutrophil engraftment was achieved on day +11, and a platelet count greater than 50 × 109/L was achieved on day +71. He is currently alive and doing well at nine months post-transplant and free of any bleeding episodes. This case suggests that unrelated donor CBT may be safe and technically feasible, even in early infancy, when an appropriately matched related or unrelated donor is unavailable. [source]

Qualitative disorders of platelets and megakaryocytes

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2005
A. T. NURDEN
Summary., Qualitative disorders of platelet function and production form a large group of rare diseases which cover a multitude of genetic defects that by and large have as a common symptom, excessive mucocutaneous bleeding. Glanzmann thrombasthenia, is enabling us to learn much about the pathophysiology of integrins and of how ,IIb,3 functions. Bernard,Soulier syndrome, an example of macrothrombocytopenia, combines the production of large platelets with a deficit or non-functioning of the major adhesion receptor of platelets, the GPIb-IX-V complex. Amino acid substitutions in GPIb,, may lead to up-regulation and spontaneous binding of von Willebrand factor as in Platelet-type von Willebrand disease. In disorders with defects in the MYH9 gene, macrothrombocytopenias are linked to modifications in kidney, eye or ear, whereas other inherited thrombocytopenias variously link a low platelet count with a propensity to leukemia, skeletal defects, learning impairment, and abnormal red cells. Defects of secretion from platelets include an abnormal , -granule formation as in the gray platelet syndrome (with marrow myelofibrosis), and of organelle biogenesis in the Hermansky,Pudlak and Chediak,Higashi syndromes where platelet dense body defects are linked to abnormalities of other lysosomal-like organelles including melanosomes. Finally, defects involving surface receptors (P2Y12, TP,) for activating stimuli, of proteins essential for signaling pathways (including Wiskott,Aldrich syndrome), and of platelet-derived procoagulant activity (Scott syndrome) show how studies on platelet disorders are helping unravel the pathways of primary hemostasis. [source]

Analysis of clinical and molecular characteristics of Wiskott,Aldrich syndrome in 24 patients from 23 unrelated Chinese families

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2010
Zhi-Yong Zhang
Zhang Z-Y, Xiao H-Q, Jiang L-P, Zhou Y, Zhao Q, Yu J, Liu W, Yang X-Q, Zhao X-D. Analysis of clinical and molecular characteristics of Wiskott,Aldrich syndrome in 24 patients from 23 unrelated Chinese families. Pediatr Allergy Immunol 2010: 21: 522,532. © 2010 John Wiley & Sons A/S The clinical data of 24 children with Wiskott,Aldrich syndrome (WAS) from 23 unrelated Chinese families were reviewed in the present study. WAS protein (WASP) expression in peripheral blood mononuclear cells was examined by flow cytometry (FCM); WASP gene was amplified by PCR and directly sequenced to analyze mutations in the WASP gene in patients and their female relatives. FCM analysis of 21 patients showed that 18 cases were WASP-negative, and three had partially WASP expression. WASP gene analysis revealed mutations in 23 patients, including five missense mutations, four nonsense mutations, four deletion mutations, three insertion mutations, six splice site mutations, and one complex mutation, among which, 20 unique mutations were detected, including seven novel mutations (168 C>A, 747,748del T, 793,797del C, 1185 ins C, Dup 1251,1267, 1277 insA and 1266 C>G; 1267,1269del C). Five WAS children underwent stem cell transplantation. After 2 months of transplantation, WASP expression was restored to normal in all five patients whereas one patient died of cytomegalovirus-induced interstitial lung disease. WASP gene analysis can make a definite diagnosis of WAS and identify mutation carriers, beneficial for timely treatment and genetic counseling for children with WAS. [source]

Early transplantation of unrelated cord blood in a two-month-old infant with Wiskott,Aldrich syndrome

Pneumatosis intestinalis in an infant undergoing bone marrow transplantation for Wiskott,Aldrich syndrome

PEDIATRIC TRANSPLANTATION, Issue 5 2001
Duygu Uçkan
Abstract: A 7-month-old patient with Wiskott,Aldrich syndrome (WAS) developed pneumatosis intestinalis (PI) in the immediate post-transplant period after receiving paternal human leucocyte antigen (HLA) phenotypically matched bone marrow (BM). PI has been described in patients with congenital or acquired immunodeficiency states and after bone marrow transplantation (BMT). To our knowledge, the condition has not been described in WAS. The underlying bowel mucosa damage as a result of the history of massive rectal bleeding, the effects of the conditioning regimen, immunosuppression, neutropenia, and infection, may all have contributed to the development of PI. Although the condition resolved by conservative management alone, the patient developed Klebsiella pneumonia sepsis, interstitial pneumonitis, failed to engraft, and died on day +66 following a second infusion of stem cells mobilized from his father's peripheral blood. [source]

Progressive multifocal leukoencephalopathy after allogeneic bone marrow transplantation for Wiskott,Aldrich syndrome

PEDIATRICS INTERNATIONAL, Issue 2 2008
Yukiharu Yasuda
No abstract is available for this article. [source]

Prenatal diagnosis and genetic analysis of Wiskott,Aldrich syndrome

PRENATAL DIAGNOSIS, Issue 12 2003
Katherine A. Siminovitch
No abstract is available for this article. [source]

Diverse genomic integration of a lentiviral vector developed for the treatment of Wiskott,Aldrich syndrome

THE JOURNAL OF GENE MEDICINE, Issue 8 2009
Julie Mantovani
Abstract Background The genomic integration of a lentiviral vector developed for the treatment of Wiskott,Aldrich syndrome (WAS) was assessed by localizing the vector insertion sites (IS) in a murine model of gene therapy for the disease. Methods Transduced hematopoietic progenitor cells were transplanted into mice or cultured in vitro. The IS were determined in the genomic DNA from blood, the bone marrow of the animals and from cultured cells. Results Sequencing vector,genomic DNA junctions yielded more than 150 IS of which 50,70% were located in transcription units. To obtain additional sequences from the population of cultured cells, we used a vector-tag concatenation technique providing 190 additional IS. Altogether, the profiles confirmed the bias for integration in transcription units. The vector did not congregate as hotspots and did not appear to target specific categories of genes. The diversity of the IS reflected the initial marking of a polyclonal population of cells. However, relatively few vector IS were found in vivo because only 30,40 unique IS were identified in each mouse using this approach. Although four to ten IS were shared by the blood and bone marrow, no common IS was found between mice or between any mouse and the cultured cells. Conclusions Taken as a whole, the pattern of genomic insertion of the WAS lentiviral vector was diverse and similar to that previously described for other HIV-1-derived lentiviral vectors. Testing cells destined for transplantation is unlikely to predict specific IS to be selected in vivo. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Wiskott,Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells

THE JOURNAL OF PATHOLOGY, Issue 4 2004
Yolanda Calle
Abstract The regulated migration and spatial localization of dendritic cells in response to environmental signals are critical events during the initiation of physiological immune responses and maintenance of tolerance. Cells deficient in the Wiskott,Aldrich syndrome protein (WASP) have been used to demonstrate the importance of the dynamic remodelling of the actin-based cytoskeleton during the selective adhesion and migration of these cells. Unlike most cell types, macrophages, dendritic cells, and osteoclasts utilize a specialized adhesive array termed the podosome in order to migrate. Podosomes are composed of many of the same structural and regulatory proteins as seen in the more commonly found focal adhesion, but are unique in their requirement for WASP. Without WASP, podosomes cannot form and the affected cells are obliged to use focal adhesions for their migratory activities. Once activated by a series of upstream regulatory proteins, WASP acts as a scaffold for the binding of the potent actin nucleating protein complex known as Arp2/3. This article reviews the available evidence that suggests that failures in the regulation of the actin cytoskeleton may contribute significantly to the immunopathology of the Wiskott,Aldrich syndrome. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

WASP plays a novel role in regulating platelet responses dependent on ,IIb,3 integrin outside-in signalling

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2010
Anna Shcherbina
Summary The most consistent feature of Wiskott Aldrich syndrome (WAS) is profound thrombocytopenia with small platelets. The responsible gene encodes WAS protein (WASP), which functions in leucocytes as an actin filament nucleating agent ,yet, actin filament nucleation proceeds normally in patient platelets regarding shape change, filopodia and lamellipodia generation. Because WASP localizes in the platelet membrane skeleton and is mobilized by ,IIb,3 integrin outside-in signalling, we questioned whether its function might be linked to integrin. Agonist-induced ,IIb,3 activation (PAC-1 binding) was normal for patient platelets, indicating normal integrin inside-out signalling. Inside-out signalling (fibrinogen, JON/A binding) was also normal for wasp-deficient murine platelets. However, adherence/spreading on immobilized fibrinogen was decreased for patient platelets and wasp-deficient murine platelets, indicating decreased integrin outside-in responses. Another integrin outside-in dependent response, fibrin clot retraction, involving contraction of the post-aggregation actin cytoskeleton, was also decreased for patient platelets and wasp-deficient murine platelets. Rebleeding from tail cuts was more frequent for wasp-deficient mice, suggesting decreased stabilisation of the primary platelet plug. In contrast, phosphatidylserine exposure, a pro-coagulant response, was enhanced for WASP-deficient patient and murine platelets. The collective results reveal a novel function for WASP in regulating pro-aggregatory and pro-coagulant responses downstream of integrin outside-in signalling. [source]