title: Two novel mutations identified in the Wiskott-Aldrich syndrome protein gene cause Wiskott-Aldrich syndrome and thrombocytopenia.
abstract: Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are rare X-linked genetic disorders caused by mutations of the Wiskott-Aldrich syndrome protein (WASP) gene. Both disorders are clinically characterized by chronic thrombocytopenia of small platelets. WAS is a more severe form of the disorder and also courses with eczema, and immune dysfunction. In the present study, we investigated two novel mutations of the WASP gene in two Spanish families with patients clinically diagnosed as having XLT and WAS, respectively. In one of the families a missense mutation in exon 12 (1488A>G), resulting in the highly conserved glutamic residue changing to glycine at position 485 (D485G), was identified in several members. Notably, a female of this family, with clinical signs of XLT, was determined as the carrier of the mutation and showed a skewed pattern of X-inactivation, preferentially inactivating the X-chromosome carrying the wild-type allele. In the case of the second family, we describe a WAS patient with a single base deletion in exon 2 (266-267delA), resulting in a frameshift (at codon 78) that creates a stop codon at amino acid 127. As a consequence, there was no WASP expression.
authors: Programa Gens i Malaltia, Centre de Regulació Genòmica CRG-UPF, Barcelona, Spain.
authors: Nuria
authors: N
authors: Andreu
authors: Núria
authors: N
authors: Matamoros
authors: Antonio
authors: A
authors: Escudero
authors: Cristina
authors: C
authors: Fillat
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010976:Platelet Count; D013921:Thrombocytopenia / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein / Q000737:chemistry / Q000235:genetics*
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein