title: Unprecedented diversity of genotypic revertants in lymphocytes of a patient with Wiskott-Aldrich syndrome.
abstract: Spontaneous somatic reversions of inherited mutations are poorly understood phenomena that are thought to occur uncommonly in a variety of genetic disorders. When molecularly characterized, revertant cells have rarely exhibited more than one revertant genotype per patient. We analyzed individual allospecific T-cell clones derived from a Wiskott-Aldrich syndrome (WAS) patient identified by flow cytometry to have 10% to 15% revertant, WAS protein-expressing lymphocytes in his blood. Genotypic analysis of the clones revealed a remarkable diversity of deletions and base substitutions resulting in at least 34 different revertant genotypes that restored expression of WASp. A large fraction of these revertant genotypes were also identified in primary T cells purified from peripheral blood. These data suggest that the use of sensitive methods may reveal the presence of wide arrays of individual genotypic revertants in WAS patients and offer opportunities for further understanding of their occurrence.
authors.affiliation: Institute for Inherited Disease Research, Newtown, PA, USA. Brian.R.Davis@uth.tmc.edu
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davis
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dicola
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Prokopishyn
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Rosenberg
authors.forename: Daniele
authors.initials: D
authors.lastname: Moratto
authors.forename: Linda M
authors.initials: LM
authors.lastname: Muul
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
authors.forename: R
authors.initials: R
authors.lastname: Michael Blaese
mesh_terms: D002999:Clone Cells; D005192:Family Health; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D016131:Lymphocyte Subsets; D008214:Lymphocytes; D009154:Mutation; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000473:pathology; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein