Altered functional balance of Gfi-1 and Gfi-1b as an alternative cause of reticular dysgenesis?

Med Hypotheses. 2010 Mar;74(3):445-8. doi: 10.1016/j.mehy.2009.09.053. Epub 2009 Nov 6.


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.

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mice
  • Models, Genetic*
  • Proto-Oncogene Proteins / genetics*
  • Repressor Proteins / genetics*
  • Severe Combined Immunodeficiency / genetics*
  • Signal Transduction / genetics*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Gfi1 protein, mouse
  • Gfi1b protein, mouse
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Transcription Factors