Missense C168T in the Wiskott–Aldrich Syndrome protein gene is a common mutation in X‐linked thrombocytopenia

Abstract

Summary. We describe a large Syrian±Lebanese family who clinically manifest X-linked thrombocytopenia (XLT). To date, five family members have undergone splenectomy with rapid and sustained normalization of their platelet numbers. Genomic analysis demonstrated that affected men in this cohort had the missense C168T (Thr45Met) mutation in exon 2 of the Wiskott±Aldrich Syndrome protein (WASp) gene. Exon 2 is the commonest site for mutations associated with XLT and mild forms of WAS, and the C168T missense mutation is the most frequent. Detection of this mutation by restriction enzyme digestion provides an efficient screening test for prompt identification and for assessment of female carrier status.

Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation

“…[9][10][11][15][16][17][18][19][20][21][22][23][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Most mutations consisted of single nucleotide substitutions, small insertions and deletions, and splice site mutations and were distributed throughout the coding region and the intron-exon junctions. Except for a large deletion involving the 5Ј untranslated region (UTR) and exons 1 and 2 (del5ЈUTR [-719]-intron2ϩ1), mutations were not found outside the coding region, and none of the WAS/XLT patients were found to lack WASP expression without having a demonstrable mutation affecting either the exons or the exon-intron junctions.…”