Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel

Wiskott-Aldrich-Syndrom

Das Wiskott-Aldrich-Syndrom ist eine x-chromosomal rezessive Erkrankung die durch Mutationen im WAS-Gen hervorgerufen wird. Klinisch äußert sich die Erkrankung durch Ekzem, Thrombozytopenie und Immundefekten. Aufgrund der Immunschwäche und der Gerinnungsstörung kommt es begleitend zu blutigen Durchfällen.

Epidemiologie

Die Inzidenz unter männlichen Lebendgeborenen liegt zwischen 1:100.000 und 1:250.000.

Management

Eine kausale und eine symptomatische Therapie sind zu unterscheiden. Die kausale Therapie besteht in einer Stammzelltransplantation; die symptomatische in einer konsequenten antibiotischen Therapie von Infektionen und Blutstillung.

Gliederung

Primärer Immundefekt
Achondroplasie-SCID-Syndrom
Autoinflammation, Antikörpermangel und Immundysregulations-Syndrom
Erbliche Infektionsanfälligkeiten
IRAK4-Mangel
Immundefekt 20
Immundefekt 21
Immundefekt 31A
Immundefekt 31B
Immundefekt 31C
Immundefekt 33
Immundefekt 38
Immundefekt 41
Kongenitale sideroblastische Anämie-B-Zell-Immundefekt-periodisches Fieber-Entwicklungsverzögerungs-Syndrom
Syndrom der zentromeren Instabilität mit Immundefizienz und Gesichtsfehlbildungen
Variable Immunmangel Typ 7
Vaskulitis durch ADA2-Mangel
Wiskott-Aldrich-Syndrom
WAS

Referenzen:

1.

Lyon MF et al. (1990) The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.

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2.

Wengler G et al. (1995) Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome.

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3.

Kwan SP et al. (1995) Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.

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4.

Villa A et al. (1995) X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.

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5.

Derry JM et al. (1994) Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.

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6.

Symons M et al. (1996) Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.

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7.

Kolluri R et al. (1996) Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.

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8.

Derry JM et al. (1995) The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome.

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9.

Schindelhauer D et al. (1996) Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.

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10.

Greer WL et al. (1996) Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome.

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11.

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12.

Puck JM et al. (1998) X inactivation in females with X-linked disease.

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13.

Waisfisz Q et al. (1999) Spontaneous functional correction of homozygous fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.

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14.

Lemahieu V et al. (1999) Novel mutations in the Wiskott-Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes.

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15.

Thompson LJ et al. () Unique and recurrent WAS gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

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16.

Devriendt K et al. (2001) Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia.

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17.

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18.

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19.

Sasahara Y et al. (2002) Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation.

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20.

Wada T et al. (2003) Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings.

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21.

ALDRICH RA et al. (1954) Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea.

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22.

Wada T et al. (2004) Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.

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23.

Du W et al. (2006) A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.

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24.

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25.

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26.

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27.

Greer WL et al. (1990) Linkage relationships of the Wiskott-Aldrich syndrome to 10 loci in the pericentromeric region of the human X chromosome.

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28.

Greer WL et al. (1989) Linkage studies of the Wiskott-Aldrich syndrome: polymorphisms at TIMP and the X chromosome centromere are informative markers for genetic prediction.

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29.

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30.

Remold-O'Donnell E et al. (1984) Characterization of a human lymphocyte surface sialoglycoprotein that is defective in Wiskott-Aldrich syndrome.

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31.

Lum LG et al. (1980) Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome.

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32.

None (1980) Splenectomy in the Wiskott-Aldrich syndrome.

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33.

Holmberg L et al. (1983) A prenatal study of fetal platelet count and size with application to fetus at risk for Wiskott-Aldrich syndrome.

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34.

Hutter JJ et al. (1981) Results of a thymic epithelial transplant in a child with Wiskott-Aldrich syndrome and central nervous system lymphoma.

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35.

Kapoor N et al. (1981) Reconstitution of normal megakaryocytopoiesis and immunologic functions in Wiskott-Aldrich syndrome by marrow transplantation following myeloablation and immunosuppression with busulfan and cyclophosphamide.

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36.

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37.

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38.

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39.

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40.

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41.

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42.

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43.

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44.

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45.

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46.

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47.

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48.

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49.

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50.

Shapiro RS et al. (1978) Wiskott-Aldrich syndrome: detection of carrier state by metabolic stress of platelets.

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51.

Parkman R et al. (1978) Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation.

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52.

Filipovich AH et al. (1979) Fatal arteritis as a complication of Wiskott-Aldrich syndrome.

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53.

Meropol NJ et al. (1992) Coincident Kaposi sarcoma and T-cell lymphoma in a patient with the Wiskott-Aldrich syndrome.

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54.

Greer WL et al. (1992) The Wiskott-Aldrich syndrome: refinement of the localization on Xp and identification of another closely linked marker locus, OATL1.

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55.

Simon HU et al. (1992) Evidence for defective transmembrane signaling in B cells from patients with Wiskott-Aldrich syndrome.

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56.

Kwan SP et al. (1991) Localization of the gene for the Wiskott-Aldrich syndrome between two flanking markers, TIMP and DXS255, on Xp11.22-Xp11.3.

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57.

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58.

De Saint-Basile G et al. (1991) X-linked thrombocytopenia and Wiskott-Aldrich syndrome: similar regional assignment but distinct X-inactivation pattern in carriers.

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59.

Brochstein JA et al. (1991) Marrow transplantation from human leukocyte antigen-identical or haploidentical donors for correction of Wiskott-Aldrich syndrome.

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60.

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61.

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62.

de Saint Basile G et al. (1989) Close linkage of hypervariable marker DXS255 to disease locus of Wiskott-Aldrich syndrome.

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63.

Schwartz M et al. (1989) First-trimester diagnosis of Wiskott-Aldrich syndrome by DNA markers.

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64.

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65.

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66.

Fearon ER et al. (1988) Carrier detection in the Wiskott Aldrich syndrome.

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67.

Peacocke M et al. (1987) Linkage of the Wiskott-Aldrich syndrome with polymorphic DNA sequences from the human X chromosome.

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68.

Mentzer SJ et al. (1987) Sialophorin, a surface sialoglycoprotein defective in the Wiskott-Aldrich syndrome, is involved in human T lymphocyte proliferation.

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69.

Standen GR et al. (1986) Inherited thrombocytopenia, elevated serum IgA and renal disease: identification as a variant of the Wiskott-Aldrich syndrome.

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70.

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71.

None (1967) Wiskott-Aldrich syndrome: clinical, immunologic, and pathologic observations.

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72.

Cooper MD et al. (1968) Wiskott-Aldrich syndrome. An immunologic deficiency disease involving the afferent limb of immunity.

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73.

Blaese RM et al. (1968) The Wiskott-Aldrich syndrome. A disorder with a possible defect in antigen processing or recognition.

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74.

Bach FH et al. (1968) Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome.

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75.

Weiden PL et al. (1972) Hereditary thrombocytopenia: relation to Wiskott-Aldrich syndrome with special reference to splenectomy. Report of a family and review of the literature.

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76.

McEnery G et al. (1973) Wiskott-Aldrich syndrome associated with idiopathic infantile cortical hyperostosis (Caffey's disease).

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77.

Diaz-Buxo JA et al. (1974) Wiskott-Aldrich syndrome in an adult.

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78.

Gutenberger J et al. (1970) Familial thrombocytopenia, elevated serum IgA levels and renal disease. A report of a kindred.

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79.

Blaese RM et al. (1971) Hypercatabolism of IgG, IgA, IgM, and albumin in the Wiskott-Aldrich syndrome. A unique disorder of serum protein metabolism.

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80.

Levin AS et al. (1970) Wiskott-Aldrich syndrome, a genetically determined cellular immunologic deficiency: clinical and laboratory responses to therapy with transfer factor.

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81.

ten Bensel RW et al. (1966) The development of malignancy in the course of the Aldrich syndrome.

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82.

Gealy WJ et al. (1980) Allelic exclusion of glucose-6-phosphate dehydrogenase in platelets and T lymphocytes from a Wiskott-Aldrich syndrome carrier.

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83.

Parkman R et al. () Surface protein abnormalities in lymphocytes and platelets from patients with Wiskott-Aldrich syndrome.

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84.

Ochs HD et al. (1980) The Wiskott-Aldrich syndrome: studies of lymphocytes, granulocytes, and platelets.

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85.

Orphanet article

Orphanet ID 906 [^]
86.

OMIM.ORG article

Omim 301000 [^]
87.

Wikipedia Artikel

Wikipedia DE (Wiskott-Aldrich-Syndrom) [^]
Update: 10. Mai 2019