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
Erbliche Infektionsanfälligkeiten
Immundefekt 21
Immundefekt 31A
Immundefekt 31B
Immundefekt 31C
Syndrom der zentromeren Instabilität mit Immundefizienz und Gesichtsfehlbildungen
Wiskott-Aldrich-Syndrom
WAS

Referenzen:

1.

Boztug K et. al. (2010) Stem-cell gene therapy for the Wiskott-Aldrich syndrome.

[^]
2.

Boztug K et. al. (2008) Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome.

[^]
3.

Dobbs AK et. al. (2007) A possible bichromatid mutation in a male gamete giving rise to a female mosaic for two different mutations in the X-linked gene WAS.

[^]
4.

Binder V et. al. (2006) The genotype of the original Wiskott phenotype.

[^]
5.

Puck JM et. al. (2006) Lessons from the Wiskott-Aldrich syndrome.

[^]
6.

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.

[^]
7.

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

[^]
8.

VAN DEN BOSCH J et. al. (1964) [THE ALDRICH SYNDROME; A CLINICAL AND GENETIC STUDY OF SEVERAL DUTCH FAMILIES].

[^]
9.

GELZER J et. al. (1961) [Wiskott-Aldrich syndrome].

[^]
10.

None (1959) Methodology in human genetics.

[^]
11.

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

[^]
12.

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

[^]
13.

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

[^]
14.

Lutskiy MI et. al. (2002) Wiskott-Aldrich syndrome in a female.

[^]
15.

Wada T et. al. (2001) Somatic mosaicism in Wiskott--Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.

[^]
16.

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

[^]
17.

Yamada M et. al. (2000) Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells.

[^]
18.

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

[^]
19.

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

[^]
20.

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

[^]
21.

Yamada M et. al. (1999) Flow cytometric analysis of Wiskott-Aldrich syndrome (WAS) protein in lymphocytes from WAS patients and their familial carriers.

[^]
22.

Giliani S et. al. (1999) Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis.

[^]
23.

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

[^]
24.

Parolini O et. al. (1998) X-linked Wiskott-Aldrich syndrome in a girl.

[^]
25.

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

[^]
26.

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.

[^]
27.

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.

[^]
28.

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

[^]
29.

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

[^]
30.

Notarangelo LD et. al. (1993) Application of molecular analysis to genetic counseling in the Wiskott-Aldrich syndrome (WAS).

[^]
31.

Knox-Macaulay HH et. al. (1993) X linked recessive thrombocytopenia.

[^]
32.

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

[^]
33.

Sullivan KE et. al. (1994) A multiinstitutional survey of the Wiskott-Aldrich syndrome.

[^]
34.

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

[^]
35.

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.

[^]
36.

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

[^]
37.

Prchal JT et. al. (1980) Wiskott-Aldrich syndrome: cellular impairments and their implication for carrier detection.

[^]
38.

Spitler LE et. al. (1980) Nephropathy in the Wiskott-Aldrich syndrome.

[^]
39.

Perry GS et. al. (1980) The Wiskott-Aldrich syndrome in the United States and Canada (1892-1979).

[^]
40.

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.

[^]
41.

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

[^]
42.

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

[^]
43.

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

[^]
44.

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

[^]
45.

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

[^]
46.

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

[^]
47.

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

[^]
48.

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

[^]
49.

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

[^]
50.

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

[^]
51.

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

[^]
52.

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

[^]
53.

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

[^]
54.

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

[^]
55.

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.

[^]
56.

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

[^]
57.

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

[^]
58.

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

[^]
59.

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

[^]
60.

Corash L et. al. (1985) Platelet-associated immunoglobulin, platelet size, and the effect of splenectomy in the Wiskott-Aldrich syndrome.

[^]
61.

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

[^]
62.

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

[^]
63.

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

[^]
64.

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

[^]
65.

Abinun M et. al. (1988) Infantile cortical hyperostosis associated with the Wiskott-Aldrich syndrome.

[^]
66.

Kwan SP et. al. (1988) Genetic mapping of the Wiskott-Aldrich syndrome with two highly-linked polymorphic DNA markers.

[^]
67.

Fischer A et. al. (1986) Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985.

[^]
68.

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

[^]
69.

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

[^]
70.

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.

[^]
71.

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

[^]
72.

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

[^]
73.

Notarangelo LD et. al. (1991) Presentation of Wiskott Aldrich syndrome as isolated thrombocytopenia.

[^]
74.

Arveiler B et. al. (1990) Germ-line mosaicism simulates genetic heterogeneity in Wiskott-Aldrich syndrome.

[^]
75.

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

[^]
76.

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

[^]
77.

Notarangelo LD et. al. (1991) Analysis of X-chromosome inactivation and presumptive expression of the Wiskott-Aldrich syndrome (WAS) gene in hematopoietic cell lineages of a thrombocytopenic carrier female of WAS.

[^]
78.

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.

[^]
79.

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

[^]
80.

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

[^]
81.

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

[^]
82.

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

[^]
83.

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

[^]
84.

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

[^]
Update: 26. September 2018