Cathepsin C Gene Mutations In Twins With Aggressive Periodntitis

Background: Aggressive periodontitis is a kind of disease which is characterized by fast periodontal attachment loss and alveolar bone destruction. It can be divided into generalized and localized, and has significant difference from chronic periodontitis. Its characteristics are: In addition to suffering from periodontitis, patients are physically healthy; they have fast periodontal attachment loss and bone destruction; significant shifting of teeth, a familial aggregation and etc. There are many factors that can cause the disease, the main pathogens is Actinobacillus actinomycetemcomitans (Aa), it can be extracted from 90%-100% patients'subgingival plaque. Some patients may have a ratio increase of other patogens such as Porphyromonas gingivalis (Pg) strains.Inflammatory mediators and cytokines play a major role of mediation in process of the destruction of local periodontal tissue. Peripheral blood mononuclear cells and neutral polymorphonuclear leukocyte in periodontitis patient have chemotactic function decreased and swallowing dysfunction. Serum C-reactive protein and tumor necrosis factor-αwould increase. In addition, other factors like genetic and environmental factors also would play a certain role in the whole process.In present study, it's normally considered that the decreased activity of protein that caused by CTSC gene mutation may result in aggressive periodontitis, but the mutation point varies in different families and there are even some families do not have mutation at all. We are observing a pair of twins with aggressive periodontitis for 3 years, using clinical diagnosis, treatment, laboratory tests, sample collection and CTSC gene sequencing methods in order to get a further understanding of the cause of this disease.Part 1 The clinical data collection of patients with aggressive periodontitis twins, periodontal examination and other special inspectionWe use the routine clinical examination, periodontal special examination and other special inspection methods on a pair of twins who both have aggressive periodontitis in order to make an explicit diagnosis. The patients are physically healthy, no development abnormalitis, all remaining teeth are loosingⅡ-Ⅲdegree, severe bone loss of alveolar bone, gingival swelling, congestion and pyorrhea. Their parents are fourth generation inbreeding, no abnormality in oral examination and no systemic disease. We are diagnosing the twins to be aggressive periodontitis patients, and they can provide us some basic gene type for the pathopoiesia gene selection in the next experiments.Part 2 Sample collection from patients'family, genomic extraction and CTSC gene detection.Experiment 1, collection of peripheral blood from 5 people of 2 generation, who are the family of aggressive periodontitis patients in Ankang, Shanxi China. DNA was successfully extracted and prepared for the next step of gene mutation studies.Experiment 2, as the research went through, we chose cathepsin C as the primary candidate gene for this disease. Gene mutations were found in the third exon of CTSC gene in patients and their families by using polymerase chain reaction PCR and DNA sequencing.Results: The CTSC gene mutation were found in the twin patients with aggressive periodontitis and their family, the stop was c.394C>G, R132G, a single peak pattern (G) was shown in sequencing map. This is a new mutation type and it results in a mistranslation from conservative arginine into glycine. But the twin's brother and parents, who have the heterozygous mutation in the same spot c.394C>G, do not have the similar clinical performance of periodontal disease. We can initially speculate that it may be the mutation happened in R132G that caused the decreased activity of CTSC protein which leads to the disease. Specific mechanism remains to be further studied.