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Clinical and Experimental Immunology Apr 2000
Review
Topics: Animals; Humans; Wiskott-Aldrich Syndrome
PubMed: 10759756
DOI: 10.1046/j.1365-2249.2000.01193.x -
Clinical Reviews in Allergy & Immunology Feb 2001
Review
Topics: Age Factors; Humans; Protein Structure, Tertiary; Wiskott-Aldrich Syndrome
PubMed: 11269229
DOI: 10.1385/CRIAI:20:1:61 -
Springer Seminars in Immunopathology 1998
Review
Topics: Age Factors; Animals; Blotting, Western; Chromosome Mapping; Female; Genotype; Humans; Male; Mice; Mutation; Phenotype; Prenatal Diagnosis; Proteins; Thrombocytopenia; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 9618767
DOI: 10.1007/BF00792601 -
Seminars in Hematology Oct 1998In 1937, Wiskott described three brothers with congenital thrombocytopenia, bloody diarrhea, eczema, and recurrent ear infections. Seventeen years later, Aldrich showed... (Review)
Review
In 1937, Wiskott described three brothers with congenital thrombocytopenia, bloody diarrhea, eczema, and recurrent ear infections. Seventeen years later, Aldrich showed X-linked (a gene carried on the X chromosome) inheritance. Subsequently, the characteristic immune defects of Wiskott-Aldrich syndrome (WAS) were reported, including lymphopenia, lymphocyte depletion in the thymus, T-dependent pericortical areas of lymph nodes, defective delayed type hypersensitivity, and failure to produce antibodies to polysaccharides and to a variety of bacterial, protein, and viral antigens. The consistent platelet abnormalities were explained by ineffective thrombocytopoiesis. The increased risk of autoimmune diseases and malignancies was recognized. In addition to the classic WAS phenotype, a milder form designated as hereditary X-linked thrombocytopenia (XLT) has been described. The genes for both WAS and XLT have been mapped to Xp11.22 and sequence analysis has identified mutations of the same gene in both phenotypes. The gene coding for the WAS protein (WASP) is composed of 12 exons containing 1,823 base pairs and encodes a 502-amino acid protein. WASP is expressed in the cytoplasm of all hematopoietic stem cell-derived lineages. Although the precise function of WASP is unknown, several unique binding domains have been identified, and WASP appears to play a critical role in signal transduction by interacting with SH3-containing molecules and in the regulation of the cytoskeletal reorganization. The identification of the WASP gene allows the diagnosis of WAS on a molecular basis, carrier detection, and prenatal diagnosis. Treatment is largely symptomatic and includes antibiotics, prophylactic intravenous immunoglobulin (i.v.IG) and splenectomy in selected cases to reduce hemorrhages. Stem cell transplantation corrects the defect and should be considered in younger patients.
Topics: Animals; Family Health; Genetic Linkage; Humans; Proteins; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein; X Chromosome
PubMed: 9801262
DOI: No ID Found -
Otology & Neurotology : Official... Apr 2013
Topics: Humans; Infant; Male; Temporal Bone; Wiskott-Aldrich Syndrome
PubMed: 23370560
DOI: 10.1097/MAO.0b013e31827de304 -
Journal of the American Academy of... Oct 1992The Wiskott-Aldrich syndrome is an uncommon X-linked recessive disease characterized by eczema, thrombocytopenia, and immunodeficiency. The clinical features begin early... (Review)
Review
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.
Topics: Genetic Linkage; Glycosylation; Humans; Wiskott-Aldrich Syndrome; X Chromosome
PubMed: 1401301
DOI: 10.1016/0190-9622(92)70215-2 -
Ocular Immunology and Inflammation Jan 2023Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease whose optimal curative treatment is hematopoietic stem cell transplantation (HSCT). Patients with WAS may...
PURPOSE
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease whose optimal curative treatment is hematopoietic stem cell transplantation (HSCT). Patients with WAS may suffer from cytomegalovirus retinitis (CMVR) which can cause vision loss. This study is to report the progression and prognosis of patients with WAS and CMVR.
METHODS
A retrospective case series of ten patients with WAS and CMVR before and after HSCT who were referred to the Ophthalmology Department of Xinhua Hospital from June 2018 to February 2021. Progression and prognosis were recorded.
RESULTS
Five patients were diagnosed with CMVR before receiving HSCT at a median age of 10.5 months (range: 4-23 months). Eight patients developed CMVR post-transplantation with a median interval from HSCT of 3.5 months (range: 1-9 months).
CONCLUSION
Regular fundus examinations and prompt treatments in patients with WAS are therefore crucial before they receiving HSCT or approximately 3.5 months after HSCT until complete reconstitution of immune function.
Topics: Humans; Infant; Cytomegalovirus Retinitis; Wiskott-Aldrich Syndrome; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Prognosis
PubMed: 34878956
DOI: 10.1080/09273948.2021.1995762 -
Journal of Clinical Immunology Jan 2018The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder originally described by Dr. Alfred Wiskott in 1937 and Dr. Robert Aldrich in 1954 as a familial disease... (Review)
Review
The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder originally described by Dr. Alfred Wiskott in 1937 and Dr. Robert Aldrich in 1954 as a familial disease characterized by infections, bleeding tendency, and eczema. Today, it is well recognized that the syndrome has a wide clinical spectrum ranging from mild, isolated thrombocytopenia to full-blown presentation that can be complicated by life-threatening hemorrhages, immunodeficiency, atopy, autoimmunity, and cancer. The pathophysiology of classic and emerging features is being elucidated by clinical studies, but remains incompletely defined, which hinders the application of targeted therapies. At the same time, progress of hematopoietic stem cell transplantation and gene therapy offer optimistic prospects for treatment options aimed at the replacement of the defective lymphohematopoietic system that have the potential to provide a cure for this rare and polymorphic disease.
Topics: Autoimmunity; Eczema; Genes, X-Linked; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Humans; Infections; Mutation; Neoplasms; Thrombocytopenia; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 29086100
DOI: 10.1007/s10875-017-0453-z -
Current Opinion in Rheumatology Jul 2003As many as 40% of patients with Wiskott-Aldrich syndrome may eventually suffer from an autoimmune disorder, with an increased chance of developing a malignancy.... (Review)
Review
As many as 40% of patients with Wiskott-Aldrich syndrome may eventually suffer from an autoimmune disorder, with an increased chance of developing a malignancy. Vasculitides and autoimmune hemolytic anemia are the two most common autoimmune manifestations and often cause considerable morbidity and mortality, because they may require treatment with bone marrow transplantation. Insights into the mechanisms of autoimmunity have provided clues to the pathogenesis of these disorders in Wiskott-Aldrich syndrome. Chronic inflammation, interleukin-2 deficiency, and increased apoptosis may all play a possible role in the loss of peripheral tolerance to self-antigens in this disease. This article reviews the manifestations and consequences of autoimmunity in Wiskott-Aldrich syndrome, its possible mechanisms, and available treatments.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Wiskott-Aldrich Syndrome
PubMed: 12819473
DOI: 10.1097/00002281-200307000-00012 -
Clinical and Experimental Immunology Apr 2023Primary immune deficiencies (PIDs) are genetic disorders impacting the appropriate development or functioning of any portion of the immune system. The broad adoption of... (Review)
Review
Primary immune deficiencies (PIDs) are genetic disorders impacting the appropriate development or functioning of any portion of the immune system. The broad adoption of high-throughput sequencing has driven discovery of new genes as well as expanded phenotypes associated with known genes. Beginning with the identification of WAS mutations in patients with severe Wiskott-Aldrich Syndrome, recognition of WAS mutations in additional patients has revealed phenotypes including isolated thrombocytopenia and X-linked neutropenia. Likewise RAC2 patients present with vastly different phenotypes depending on the mutation-ranging from reticular dysgenesis or severe neutrophil dysfunction with neonatal presentation to later onset common variable immune deficiency. This review examines genotype-phenotype correlations in patients with WAS (Wiskott-Aldrich Syndrome) and RAC2 mutations, highlighting functional protein domains, how mutations alter protein interactions, and how specific mutations can affect isolated functions of the protein leading to disparate phenotypes.
Topics: Humans; Mutation; Phenotype; Thrombocytopenia; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein; RAC2 GTP-Binding Protein
PubMed: 36617178
DOI: 10.1093/cei/uxad001