1. ¹Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG-UPF, Passeig Marítim, 37-49, 08003 Barcelona, Spain
2. ²Unidad de Inmunología, Hospital Universitario la Paz, Madrid, Spain
3. ³Centre de Diagnosi Genètic Molecular-IRO-IDIBELL, L'Hospitalet de Llobregat, Spain
4. ⁴Unidad de Inmunología, Instituto de Biopatología y Medicina Regenarativa, Facultad de Medicina, Universidad de Granada, Granada, Spain

Correspondence: Cristina Fillat, Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG-UPF, Passeig Marítim, 37-49, 08003 Barcelona, Spain. Fax: +34-93-2240899. E-mail: cristina.fillat@crg.es

Received 28 July 2005; Accepted 7 October 2005; Published online 22 December 2005.

Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by immunodeficiency, thrombocytopenia and eczema. A broad spectrum of mutations in the WASP gene has been identified as causing the disease. In the present paper, we report on a patient affected by WAS with a novel complex mutation, characterized by a small 9 bp deletion followed by an inversion of 151 bp and a gross deletion of 4.3 kb within the Xp11.23 region. The small deletion and the inverted fragment are found in intron 11. The large deletion initiates downstream of exon 11 of the WASP gene, including exon 12, and a genomic region upstream of the promoter of the contiguous SUV39H1 gene. Expression studies of the mRNA of the patient's sample showed the presence of two aberrant transcripts that code for a protein of 519 amino acids. We demonstrate that these two transcripts differ in the 3' UTR region, and result from the use of two alternative polyadenylation signals. The severe phenotype of the patient correlates with the presence of an aberrant protein.