title: Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome.
abstract: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disorder associated with microthrombocytopenia, eczema, autoimmunity and predisposition to malignant lymphoma. Although rare, few cases of somatic mosaicism have been published in WAS patients to date. We here report on two Ukrainian siblings who were referred to us at the age of 3 and 4 years, respectively. Both patients suffered from severe WAS caused by a nonsense mutation in exon 1 of the WAS gene. In both siblings, flow cytometric analysis revealed the presence of Wiskott-Aldrich syndrome protein (WASp)-positive and WASp-negative cell populations among T and B lymphocytes as well as natural killer (NK) cells. In contrast to previously described cases of revertant mosaicism in WAS, molecular analyses in both children showed that the WASp-positive T cells, B cells, and NK cells carried multiple different second-site mutations, resulting in different missense mutations. To our knowledge, this is the first report describing somatic mosaicism in WAS patients caused by several independent second-site mutations in the WAS gene.
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Boztug
authors.forename: M
authors.initials: M
authors.lastname: Germeshausen
authors.forename: I
authors.initials: I
authors.lastname: Avedillo Díez
authors.forename: V
authors.initials: V
authors.lastname: Gulacsy
authors.forename: J
authors.initials: J
authors.lastname: Diestelhorst
authors.forename: M
authors.initials: M
authors.lastname: Ballmaier
authors.forename: K
authors.initials: K
authors.lastname: Welte
authors.forename: L
authors.initials: L
authors.lastname: Maródi
authors.forename: Li
authors.initials: L
authors.lastname: Chernyshova
authors.forename: C
authors.initials: C
authors.lastname: Klein
mesh_terms: D002675:Child, Preschool; D018389:Codon, Nonsense; D006801:Humans; D008297:Male; D009030:Mosaicism; D035781:Siblings; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein