Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.
Jin Y,
Mazza C,
Christie JR,
Giliani S,
Fiorini M,
Mella P,
Gandellini F,
Stewart DM,
Zhu Q,
Nelson DL,
Notarangelo LD,
Ochs HD.
Department of Pediatrics, University of Washington, Seattle, WA 98109, USA.
The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. X-linked thrombocytopenia (XLT) is an allelic variant of WAS which presents with a milder phenotype, generally limited to thrombocytopenia. WAS and XLT are caused by mutations of the Wiskott-Aldrich syndrome protein (WASP) gene which encodes a 502-amino acid protein, named WASP. WASP is thought to play a role in actin cytoskeleton organization and cell signaling. Here, we report the identification of 141 unique mutations, 71 not previously reported, from 227 WAS/XLT families with a total of 262 affected members. When possible we studied the effects of these mutations on transcription, RNA splicing, and protein expression. By analyzing a large number of patients with WAS/XLT at the molecular level we identified 5 mutational hotspots in the WASP gene and have been able to establish a strong association between genotype and phenotype.
PMID: 15284122 [PubMed - indexed for MEDLINE]