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DOI: 10.1055/s-0038-1650318
Mutation Spectrum in Patients with Wiskott-Aldrich Syndrome and X-linked Thrombocytopenia: Identification of Twelve Different Mutations in the WASP Gene
Publication History
Received 12 October 1995
Accepted after resubmission 05 January 1996
Publication Date:
10 July 2018 (online)
Summary
Twelve different mutations in the WASP gene were found in twelve unrelated families with Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT). Four frameshift, one splice, one nonsense mutation, and one 18-base-pair deletion were detected in seven patients with WAS. Only missense mutations were found in five patients diagnosed as having XLT. One of the nucleotide substitutions in exon 2 (codon 86) results in an Arg to Cys replacement. Two other nucleotide substitutions in this codon, R86L and R86H, have been reported previously, both giving rise to typical WAS symptoms, indicating a mutational hot spot in this codon. The finding of mutations in the WASP gene in both WAS and XLT gives further evidence of these syndromes being allelic. The relatively small size of the WASP gene facilitates the detection of mutations and a reliable diagnosis of both carriers and affected fetuses in families with WAS or XLT.
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References
- 1 Wiskott A. Familiärer, angeborener Morbus Werlhofii?. Mschr Kinderheilk 1937; 68: 212-216
- 2 Aldrich RA, Steinberg AG, Campbell DC. Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea. Pediatrics 1954; 13: 133-139
- 3 Canales L, Mauer AM. Sex-linked hereditary thrombocytopenia as a variant of Wiskott-Aldrich syndrome. New Engl J Med 1967; 277: 899-901
- 4 Cohn J, Hauge M, Andersen V, Kenningsen K, Nielsen LS, Thomsen M, Iversen T. Sex-linked hereditary thrombocytopenia with immunological defects. Hum Hered 1975; 25: 309-317
- 5 Stormorken H, Helium B, Egeland T, Abrahamsen TG, Hovig J. X-linked thrombocytopenia and thrombocytopathia; attenuated Wiskott-Aldrich syndrome. Thromb Haemost 1991; 65: 300-305
- 6 Peacocke M, Siminovitch KA. Linkage of the Wiskott-Aldrich syndrome with polymorphic DNA sequences from the human X chromosome. Proc Nat Acad Sci 1987; 84: 3430-3433
- 7 Kwan SP, Lehner T, Hagemann T, Lu B, Blaese M, Ochs H, Wedgwood R, Ott J, Craig IW, Rosen FS. Localization of the gene for the Wiskott-Aldrich syndrome between two flanking markers, TIMP and DXS255, on Xpl 1.22-Xpll.3. Genomics 1991; 10: 29-33
- 8 Cremin S, Greer WL, Bodok-Nutzati R, Schwartz M, Peacocke M, Siminovitch KA. Linkage of Wiskott-Aldrich syndrome with three marker loci, DXS426, SYP and TFE 3, which map to the Xpl 1.3-pl 1.22 region. Human Genet 1992; 88: 453-456
- 9 Donner M, Schwartz M, Carlsson KU, Holmberg L. Hereditary X-linked thrombocytopenia maps to the same chromosomal region as the Wiskott-Aldrich syndrome. Blood 1988; 72: 1849-1853
- 10 Derry JMJ, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell 1994; 78: 635-644
- 11 Kwan SP, Hagemann TL, Radtke BE, Blaese M, Rosen FS. Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene. Proc Natl Acad Sci 1995; 92: 4706-4710
- 12 Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG, Ugazio A, Vezzoni P. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nature Genet 1995; 9: 414-417
- 13 Kolluri R, Shehabeldin A, Peacocke M, Lamhonwah A-M, Teichert-Kulis-zewska K, Weissman SM, Siminovitch KA. Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus. Hum Molec Genet 1995; 4: 1119-1126
- 14 Derry JMJ, Kerns JA, Weinberg KI, Ochs HD, Volpini V, Estivill X, Walker AP, Francke U. WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia. Hum Molec Genet 1995; 4: 1127-1135
- 15 Beaudet AL, Tsui L-C. A suggested nomenclature for designating mutations. Hum Mutat 1993; 2: 245-248
- 16 Vestermark B, Vestermark S. Familial sex-linked thrombocytopenia. Acta Paediat 1964; 53: 365-370
- 17 Schwartz M, Mibashan RS, Nicolaides KH, Millar DS, Jenkins E, Rodeck CH, Ørstavik KH, Stormorken H. First-trimester diagnosis of Wiskott-Aldrich Syndrome by DNA markers. Lancet 1989; II: 1405