Analysis of a novel mutation in the C/EBPe gene and granulocytic differentiation in neutrophil-specific granule deficiency

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09642
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kanazawa University
• Principal Investigator: Wada Taizo 金沢大学, 附属病院, 講師 (30313646)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 小児科学 / 先天性免疫不全症 / 好中球二次顆粒欠損症

Outline of Final Research Achievements

Neutrophil-specific granule deficiency (SGD) is a primary immunodeficiency disease caused by mutations in a transcription factor, CCAAT/enhancer binding protein-ε (C/EBPε). We have identified a third case of genetically defined SGD. She had a novel homozygous 2-aa deletion in the leucine zipper domain of the C/EBPε gene. The mutant maintained normal cellular localization and DNA-binding activity, but was defective in protein-protein interaction with other transcription factors, resulting in a loss of transcriptional activation. Her neutrophils showed aberrant expression of monocyte markers such as CD14. These results support the importance of the leucine zipper domain of C/EBPε for its essential function, and indicate a novel molecular mechanism that leads to SGD in the patient.

Free Research Field

医歯薬学