A novel splice site mutation in the WAS gene causes Wiskott-Aldrich syndrome in two siblings of a Saudi family.

We report here on a Saudi family with two affected males with Wiskott-Aldrich syndrome (WAS), which includes mild to moderate bleeding and a low platelet count. A novel splice donor-site mutation (811 + 5 G <-- C) in intron 8 of the WAS gene (Genbank accession number NM_000377) was detected in a hemizygous status in both index cases, heterozygous in their mother and absent in the father. RNA from both index cases was transcribed and amplified with primers complementary to sequences in exons 7 and 10. A reverse transcription-polymerase chain reaction (RT-PCR) product of 688 bp (approximately 82%) was produced in addition to the normal RT-PCR product of 485 bp (approximately 18%). cDNA sequence analysis reveals an inclusion of full intron 8 sequence in the final transcript. The resultant protein is predicted to have 68 missense codons and a pre-mature stop codon at amino acid 260. This novel splice donor-site mutation was not detected in 80 normal controls (56 females and 24 males) from the same ethnic background as the index cases. Since no other mutation was detected in the WAS gene and the patients have classical symptoms of WAS, we concluded that it is highly likely that this novel mutation is responsible for the phenotype observed in these patients.