Clinical Study And Genetic Mutation Analysis Of A Family With Acatalasemia

It is increasingly evident that genetic variance is a major determinant of the differential risk for many human diseases, including periodontitis. While microbial and other environmental factors initiate and modulate periodontal disease, individuals are known to respond differently to common environmental challenges, and this differential response is influenced by the individual's genetic profile. Genes clearly play a role in the predisposition to and progression of periodontal diseases. The genetic factors might impair inflammatory and immune responses in general, and affect periodontitis experience specifically. Disorders of the periodontium are generally considered to be the end result of the response of a susceptible host to components of bacterial plaque. In contrast to the simple Mendelian inheritance, the periodontal diseases are assumed to result from the interaction of one or more genes with environmental factors.Acatalasemia is a genetic disease caused by the deficiency of catalase and is inherited as an autosomal recessive trait. Acatalasemia is also associated with oral ulceration and periodontal destruction in a small proportion of homozygous individuals. Human catalase protein is a tetramer composed of four identical subunits, each containing a heme group. The lesions of congenital erythropoietic porphyria may involve the periodontium. The catalase gene might provide limited support for a genetic contribution to disease susceptibility.ObjectiveAn ACAT family in China was reported at the first time. Here we describe a two-generation family with ACAT. We performed clinical study and genetic mutation analysis related to this family.MethodsAll members in the family were carefully evaluated related to clinical symptoms, in order to acquire the complete clinical phenotype. Based on the progress reported in this field, we selected one gene (catalase, CAT) as candidate gene, DNA sequencing was performed on all exons and the exon-intron splicing sites of the catalase gene.Results1. The characteristics of this family are as follows: (1) there are 1 affected member in two generation, one male in the second generation, and the first generations have no clinical symptoms. These feathers indicated an autosomal recessive manner; (2) there is no known history of any condition that could have caused acatalasemic or hytocatalasmic condition; (3) the onset age is 7 years old; (4) the affected member has a syndrome of oral ulcerations and gangrene, with recurrent soft tissue infection in maxillofacial region; (5) the blood catalase activities of the acatalasemic patient was 4.6% (5.2MU/L) of the normal blood catalase activity (113.3±16.5 MU/L), and the blood catalase activities of the other members in this family is 92.8 MU/L (82.1%) and 86.2MU/L (76.3%). Clinically diagnosis of ACAT is made. We have achieved good therapeutic efficacy with periodic supportive periodontal care and active antibiotic therapy.2. We carried out mutation screening of all exons and exon-intron splicing sites of the candidate gene (CAT). We find a single G to A point mutation at the fifth position of intron 4, identical to that previously found in Japan, which has spread in the Japanese population. We haven't found other new mutation.3. In discussion, we analyzed the relationship between CAT gene mutation and some associated diseases, proposed possible mechanism by which the mutation of CAT gene perform, reviewed the role of CAT gene in oxidative stress, and presented directions for further research.Conclusions1. Clinical phenotype heterogeneity exists in this ACAT family. The affected member has serious oral ulcerations and gangrene. And we find a single G to A point mutation at the fifth position of intron 4, identical to that previously found in Japan, which has spread in the Japanese population. The fifth position of intron 4 of the catalase gene may be minor hot spots for periodontitis susceptibility mutations.2. The catalase gene is associated with oxidative stress, and it is also correlate to glyco-, leipo- and proteo- metabolism, It is important to further study on catalase gene for our deep understanding of mechanisms of Diabetes Mellitus, cardiovascular disease and periodontal diseases.