Mutation Spectrum in Patients with Wiskott-Aldrich Syndrome and X-linked Thrombocytopenia: Identification of Twelve Different Mutations in the WASP Gene

Marianne Schwartz; Albert Békássy; Mikael Donnér; Thomas Hertel; Stefan Hreidarson; Gitte Kerndrup; Helge Stormorken; Tore Stokland; Lisbeth Tranebjcerg; Karen Helene Ørstavik; Flemming Skovby

doi:10.1055/s-0038-1650318

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(04): 546-550
DOI: 10.1055/s-0038-1650318

Original Article

Schattauer GmbH Stuttgart

Mutation Spectrum in Patients with Wiskott-Aldrich Syndrome and X-linked Thrombocytopenia: Identification of Twelve Different Mutations in the WASP Gene

Authors

Marianne Schwartz

¹The Department of Clinical Genetics, Laboratory of Molecular Genetics, University Hospital, Rigshospitalet, Copenhagen, Denmark
Albert Békássy

²Department of Paediatrics, University Hospital, Lund, Sweden
Mikael Donnér

²Department of Paediatrics, University Hospital, Lund, Sweden
Thomas Hertel

³Department of Growth and Reproduction, University Hospital, Rigshospitalet, Copenhagen, Denmark
Stefan Hreidarson

⁴State Diagnostic and Counselling Centre, Reykjavik, Iceland
Gitte Kerndrup

⁵Department of Pathology and Paediatrics, University Hospital, Odense, Denmark
Helge Stormorken

⁶Institute for Research, Internal Medicine, Rikshospitalet, Oslo, Norway
Tore Stokland

⁷Department of Paediatrics, University Hospital, Trohnsø, Norway
Lisbeth Tranebjcerg

⁸Department of Medical Genetics, University Hospital, Tromso, Norway
Karen Helene Ørstavik

⁹Department of Medical Genetics, Ulleval University Hospital, Oslo, Norway
Flemming Skovby

¹The Department of Clinical Genetics, Laboratory of Molecular Genetics, University Hospital, Rigshospitalet, Copenhagen, Denmark

Abstract

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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

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