title: Altered functional balance of Gfi-1 and Gfi-1b as an alternative cause of reticular dysgenesis?
abstract: Reticular dysgenesis (RD) is a rare form of severe combined immunodeficiency (SCID). The underlying genetic defect for most cases of RD was recently identified in the gene encoding adenylate kinase 2 (AK2). However, rare patients with RD and no mutations in AK2 exist, suggesting that mutations in other genes may also cause RD. Although rare, RD has a devastating presentation involving severe neutropenia and T cell lymphopenia, in addition to life non-threatening, but still disabling sensori-neural deafness. An identical phenotype is observed in mice deficient for growth factor independence-1 (Gfi-1) or transgenic for Gfi-1b, related nucleoproteins with opposing, antagonizing roles in development. We hypothesize that a genetically based, altered functional balance between these two factors may be an alternative cause of RD.
authors.affiliation: Department of Medicine, New York University Langone Medical Center, 530 First Avenue, New York, NY 10016, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Barjaktarevic
authors.forename: Jelena
authors.initials: J
authors.lastname: Maletkovic-Barjaktarevic
authors.forename: Naynesh R
authors.initials: NR
authors.lastname: Kamani
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanovic
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; C486395:Gfi1b protein, mouse; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors