title: Identification and characterization of a novel splice-site mutation in a patient with Wiskott-Aldrich syndrome.
abstract: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by immunodeficiency, eczema, and thrombocytopenia with small platelets. A wide spectrum of mutations in the Wiskott-Aldrich syndrome protein ( WASP) gene have been identified as causative of the disease. In the present paper, we report on a family with a boy affected by WAS, with a splice-site mutation caused by a T to G substitution in the +2 position of intron 6 (IVS6+2T>G). Expression studies performed in COS-7 and U-937 cells showed that the mutation affected the normal splicing process. As a consequence, an abnormally long transcript of 38 nucleotides is generated. Such missplicing is probably due to the activation of a cryptic splice donor site located 38 nt downstream of exon 6. The translation of such aberrant mRNA will produce a truncated protein with a premature stop at codon 190. Thus, a novel splice-site mutation is reported in a patient with a mild WAS phenotype.
authors.affiliation: Programa Gens i Malaltia, Centre de Regulació Genòmica, 37-49 Passeig Marítim, 08003, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Andreu
authors.forename: Carmen
authors.initials: C
authors.lastname: Carreras
authors.forename: Félix
authors.initials: F
authors.lastname: Prieto
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Victor
authors.initials: V
authors.lastname: Volpini
authors.forename: Cristina
authors.initials: C
authors.lastname: Fillat
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D015870:Gene Expression; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D022821:RNA Splice Sites / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites