A novel single-base deletion of the RUNX Family Transcription Factor 2 gene associated with cleidocranial dysplasia.

Abstract

Cleidocranial dysplasia (CCD) is a rare, autosomal dominant hereditary disorder characterized by skeletal malformations and dental abnormalities. The purpose of this study was to explore the functional role of a novel mutation in the pathogenesis of CCD. Genomic DNA was extracted from peripheral blood mononuclear cells collected from family members of a Chinese patient with CCD. An analysis of their RUNX Family Transcription Factor 2 (RUNX2) gene sequences was performed by PCR amplification and Sanger sequencing. The function of the mutant RUNX2 was studied by bioinformatics, real-time PCR, western blotting, and subcellular localization analysis. Sanger sequencing identified a novel single-base deletion (NM_001024630.4:c.132delG;NP_001019801.3: Val45Trpfs* 99) in the RUNX2 gene present in the Chinese patient with CCD. In vitro, functional studies showed altered protein localization and increased expression of mutant RUNX2 mRNA and mutant Runt-related transcription factor 2 (RUNX2). Luciferase reporter assay demonstrated that the novel RUNX2 mutations significantly increased the transactivation activity of RUNX2 on the osteocalcin gene promoter. In conclusion, we identified a patient with sporadic CCD carrying a novel deletion/frameshift mutation of the RUNX2 gene and performed screening and functional analyses to determine the cause of the CCD phenotype. This study provides new insights into the pathogenesis of CCD.3.

• Authors: Yuhua Pan, Wanyu Lu, Weidong Meng, Wenxiao Liao, Aiqin Hu, Buling Wu, Fu Xiong
• Journal: European journal of oral sciences (Eur J Oral Sci) Vol. 131 Issue 1 Pg. e12910 (02 2023) ISSN: 1600-0722 [Electronic] England
• PMID: 36598486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.

Chemical References

• Core Binding Factor Alpha 1 Subunit

Topics

• Humans
• Cleidocranial Dysplasia (genetics, pathology)
• Core Binding Factor Alpha 1 Subunit (genetics, metabolism)
• Leukocytes, Mononuclear (metabolism, pathology)
• Frameshift Mutation
• Phenotype
• Mutation