title: Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.
abstract: We previously reported on a 43-year-old patient with Wiskott-Aldrich syndrome (WAS) who experienced progressive clinical improvement and revertant T-cell mosaicism. Deletion of the disease-causing 6-bp insertion was hypothesized to have occurred by DNA polymerase slippage. We now describe 2 additional patients from the same family who also had revertant T lymphocytes that showed selective in vivo advantage. Somatic mosaicism was demonstrated on leukocytes cryopreserved in the first patient when he was 22 years old, 11 years before his death from kidney failure. The second patient is now 16 years old, has a moderate clinical phenotype, and developed revertant cells after the age of 14 years. These results support DNA polymerase slippage as a common underlying mechanism, and they indicate that T-cell mosaicism may have different clinical effects in WAS.
authors.affiliation: Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bldg 49, Rm 3A20, MSC 4442, 49 Convent Drive, Bethesda, MD 20892-4442, USA.
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.forename: Shepherd H
authors.initials: SH
authors.lastname: Schurman
authors.forename: G Jayashree
authors.initials: GJ
authors.lastname: Jagadeesh
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Garabedian
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
mesh_terms: D000293:Adolescent; D000328:Adult; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D009030:Mosaicism; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein