Mutation spectrum in patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia: identification of twelve different mutations in the WASP gene

• Published in: Thrombosis and haemostasis Vol. 75; no. 4; p. 546
• Main Authors: Schwartz, M, Békássy, A, Donnér, M, Hertel, T, Hreidarson, S, Kerndrup, G, Stormorken, H, Stokland, T, Tranebjaerg, L, Orstavik, K H, Skovby, F
• Format: Journal Article
• Language: English
• Published: Germany 01.04.1996
• Subjects: Base Sequence; Cloning, Molecular; Female; Genetic Counseling; Genetic Linkage; Genotype; Humans; Male; Molecular Sequence Data; Mutation; Pedigree; Phenotype; Predictive Value of Tests; Prenatal Diagnosis; Thrombocytopenia - diagnosis; Thrombocytopenia - genetics; Wiskott-Aldrich Syndrome - diagnosis; Wiskott-Aldrich Syndrome - genetics; X Chromosome
• ISSN: 0340-6245
• DOI: 10.1055/s-0038-1650318

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.