Journal article
Aggressive Periodontitis: A case report with exome sequencing and functional characterization of identified variant
Nigerian Dental Journal, Vol.32(2), pp.4-12
06/25/2024
DOI: 10.61172/ndj.v32i2.282
Abstract
Aggressive periodontitis (AgP) is characterized by rapid and progressive destruction of the periodontal tissues and eventual tooth loss. Genetic risk contributions have been explored and rare mutations in NOD2 were reported. Sequencing analysis of the coding regions of NOD2 was conducted using individuals of African ancestry, to identify the pathogenic protein-altering variants in individuals with AgP using: 1) In Silico tools and clinical variant classification system; 2) IF staining to understand the expression pattern, and 3) In vitro cell based assay to understand the variant protein function. We discovered a novel nonsense NOD2 variant (c.835G>T; p.Glu279Ter) ; a truncating protein variant that is clinically pathogenic, and the gene-product lacks domains regulating inflammatory responses. Murine studies suggest that this gene contributes to tooth development. In vitro analysis suggests a dominant-negative effect of the variant. NOD2 gene is expressed in the immune cells and periodontal tissues and regulates the inflammatory response within this tissue. This truncating variant found in one African family, which results in a dominant-negative effect, could explain the exacerbated immune response to pathogens in the pathogenesis of this periodontal disease.
Details
- Title: Subtitle
- Aggressive Periodontitis: A case report with exome sequencing and functional characterization of identified variant
- Creators
- Waheed Awotoye - University of IowaPatricia Ayanbadejo - University of IowaSteven Eliason - University of IowaKehinde Umeizudike - Lagos University Teaching HospitalAyodele Ogundana - Lagos University Teaching HospitalDan Su - University of IowaTadkamol Krongbaramee - University of IowaEmmanuel Aladenika - University of IowaAzeez Alade - University of IowaAbimbola Oladayo - University of IowaAbdul-Warith Akinshipo - University of LagosTamara Busch - University of IowaWasiu Adeyemo - University of LagosBrad Amendt - University of IowaAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nigerian Dental Journal, Vol.32(2), pp.4-12
- DOI
- 10.61172/ndj.v32i2.282
- ISSN
- 0189-1006
- eISSN
- 0189-1006
- Language
- English
- Date published
- 06/25/2024
- Academic Unit
- Orthodontics; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984652159802771
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