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: Igor Barjaktarevic, Jelena Maletkovic-Barjaktarevic, Naynesh R Kamani, Stanislav Vukmanovic
• Journal: Medical hypotheses (Med Hypotheses) Vol. 74 Issue 3 Pg. 445-8 (Mar 2010) ISSN: 1532-2777 [Electronic] United States
• PMID: 19896777 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

• 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)