title: The c.273+11dup genetic change in the WAS gene is a functionally neutral polymorphism.
abstract: Several pediatric patients showing symptoms consistent with the Wiskott-Aldrich syndrome (WAS) were referred to us and turned out to display the c.273+11dup change in the WAS gene. It consisted of the insertion of one C in an unusual tract of 7C near the intron 2 donor splicing site of the WAS gene. In the patients, non-synonymous WAS mutations were found twice only and one mutation was elucidated in RUNX1. In the absence of a non-synonymous mutation in the WAS gene, the c.273+11dup change affected neither the levels nor the sequence of WAS mRNA. In the presence of a non-synonymous WAS mutation, the c.273+11dup alteration failed to worsen the expected phenotype. Minor splicing abnormalities concerning exon 10 were observed both in WAS patients, and in healthy individuals carrying or not carrying the c.273+11dup. The c.273+11dup change was encountered four times in 107 normal male and female controls (172 alleles tested: 2.3%), and eight times in a series of 248 male patients (248 alleles tested: 3.2%). We conclude that the presence of the additional C in the WAS gene is a functionally neutral polymorphism.
authors.affiliation: Molecular Immunology and Innovative Biotherapies, INSERM U951, Généthon, Evry, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Jeanson-Leh
authors.forename: Sabine
authors.initials: S
authors.lastname: Charrier
authors.forename: Alexis
authors.initials: A
authors.lastname: Proust
authors.forename: Chrystele
authors.initials: C
authors.lastname: Bilhou-Nabéra
authors.forename: Rémi
authors.initials: R
authors.lastname: Favier
authors.forename: Caroline
authors.initials: C
authors.lastname: Deswarte
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Anne
authors.initials: A
authors.lastname: Galy
authors.forename: Jean
authors.initials: J
authors.lastname: Delaunay
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D020440:Gene Duplication; D006801:Humans; D007438:Introns; D009154:Mutation; D011110:Polymorphism, Genetic; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*
chemical_list: D017931:DNA Primers; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein