Susceptibility of Grade C Molar Incisor Pattern Periodontitis in Children and Adolescents (CMIP)

Grade C periodontitis (formerly aggressive periodontitis) is a rare, rapidly progressing disease affecting young individuals and often clustering in families. This multi-center study will analyze global cases to identify genetic susceptibility, host-response pathways, and microbial profiles using whole-exome sequencing, epithelial transcriptomics, and metagenomic analysis to better understand disease mechanisms and risk.

This research seeks to better understand the biological factors that contribute to Grade C Molar-Incisor Pattern Periodontitis (C-MIP) by examining patients and families from the United States, Brazil, Africa and Europe. The study will compare individuals with C-MIP with their healthy siblings and unrelated healthy controls to investigate the genetic, inflammatory and microbial factors associated with the disease.

The study has three primary aims:

• Aim 1: Exome sequencing — Analyze salivary DNA to identify genetic variants shared among individuals with C-MIP and their families, then validate those variants through a case-control study.
• Aim 2: Transcriptome and local inflammation — Analyze salivary RNA to examine gene expression and local inflammatory markers, with findings further validated through tissue biopsies.
• Aim 3: Microbiome profiling — Analyze plaque DNA to characterize the oral microbiome and investigate different strains of Aggregatibacter actinomycetemcomitans (Aa).

Researchers will then integrate and analyze data across these areas to better understand how genetic susceptibility, the body's inflammatory response and the oral microbiome may interact in the development and progression of C-MIP.

This data collectively will provide us with acomprehensive understanding of susceptibility pathways leading to C/MIP.Future work will utilize these data to find important targets for earlyprevention of disease onset or progression in susceptible families, as well asrecurrence of disease in previously treated cases. Importantly, the data willhighlight risk factors and disease mechanisms unique to specificpopulations, which will be critical for the development of individualizedtherapies in the future.​

The study is funded by the National Institute of Health (NIH)

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Graças YTD, Miguel MMV, Casarin RCV, Santamaria MP, Mishra P, Shaddox LM. Grade C molar-incisor pattern periodontitis classification and its challenges. J Periodontol. 2026;e70119. https://doi.org/10.1002/jper.70119