Identification of WASP mutations in 14 Spanish families with Wiskott-Aldrich syndrome

The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency caused b y mutations in the WASP gene. The disease is known to be associated with ex tensive clinical variability, and mutation studies indicate that genotypes are also highly variant among WAS patients, In this study, we performed mut ation analysis of the WASP gene in 14 unrelated Spanish families by single strand conformation analysis (SSCA) and sequencing, resulting in the identi fication of a novel mutation and nine known mutations. No mutation was iden tified in one family. The ten different mutations include point mutations r esulting in amino acid substitutions, stop codons, and small deletions and insertions causing frameshifts, Missense mutations were preferentially loca ted in the amino-terminal part of the protein, exons 2 and 4, whereas stop and frameshift mutations were located in the carboxyl-terminal region, exon s 10 and 11, However, in two families, two missense mutations in exon 11 we re identified. Our study demonstrates that WASP genotypes have some concord ance with the patients' phenotypes, although mutation 1019delC, identified in a family with several affected members, resulted in high intrafamilial c linical variability. (C) 2001 Wiley-Liss, Inc.