Aggressive Periodontitis with Neutropenia Caused byMMD2Mutation

Abstract

AbstractAggressive periodontitis causes rapid periodontal tissue destruction and is a disease that occurs at a young age and runs in the patient’s family. Here, we revealed a heterozygous A116V missense mutation in the gene encoding monocyte to macrophage differentiation associated 2 (MMD2) protein in a Japanese family with aggressive periodontitis and neutropenia. Analyses of patients’ peripheral blood revealed a low number of neutrophils but abundant quantity of CD34+hematopoietic stem and progenitor cells (HSPCs). Moreover, mutantMmd2mice showed severe alveolar bone loss and neutropenia. In patients and mutantMmd2mice, differentiation of HSPCs into granulocytes was also impeded, and their granulocytes were functionally impaired. Taken together, A116V mutation inMMD2gene induced mild neutropenia and slightly limited the immune defense response. Our studies suggested that aggressive periodontitis in association with A116VMMD2mutation constitutes a new immune system defect that belongs to the same spectrum of severe congenital neutropenia.