title: A novel Wiskott-Aldrich syndrome protein (WASP) complex mutation identified in a WAS patient results in an aberrant product at the C-terminus from two transcripts with unusual polyA signals.
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.
authors.affiliation: Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG-UPF, Passeig Marítim, 37-49, 08003, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Andreu
authors.affiliation: Unidad de Inmunología, Hospital Universitario la Paz, Madrid, Spain.
authors.forename: Maricruz
authors.initials: M
authors.lastname: García-Rodríguez
authors.affiliation: Centre de Diagnosi Genètic Molecular-IRO-IDIBELL, L'Hospitalet de Llobregat, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Volpini
authors.affiliation: Unidad de Inmunología, Instituto de Biopatología y Medicina Regenarativa, Facultad de Medicina, Universidad de Granada, Granada, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Frecha
authors.affiliation: Unidad de Inmunología, Instituto de Biopatología y Medicina Regenarativa, Facultad de Medicina, Universidad de Granada, Granada, Spain.
authors.forename: Ignacio J
authors.initials: IJ
authors.lastname: Molina
authors.affiliation: Unidad de Inmunología, Hospital Universitario la Paz, Madrid, Spain.
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fontan
authors.affiliation: Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG-UPF, Passeig Marítim, 37-49, 08003, Barcelona, Spain. cristina.fillat@crg.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fillat
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D007446:Chromosome Inversion / Q000235:genetics; D017931:DNA Primers; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011061:Poly A / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D013030:Spain; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D051316:Wiskott-Aldrich Syndrome Protein; D011061:Poly A