Novel mutations in GJA1 in two Brazilian families with oculodentodigital dysplasia.

Oculodentodigital dysplasia (ODDD; MIM #164200), a rare genetic disorder characterized by abnormal craniofacial, dental, ocular, and digital features, is caused by mutations in GJA1 (gap junction alpha-1) gene and inherited in an autosomal dominant pattern. However, an autosomal recessive pattern is also reported. Here we described 2 families with members affected by ODDD. In the first family, the c.752G>C (p.S251T) and c.848C>T (p.P283L) heterozygous missense mutations and the c.825C>T (p.T275T) silent mutation were identified in the proband, which showed mild ODDD phenotypes, and in his mother, which displayed hemolytic anemia and thrombocytopenia. In the second family, the patients displayed typical features of ODDD, and Sanger sequencing identified a novel homozygous c.604C>T (p.R202C) missense mutation, whereas the parents carried the mutation. Together, these findings suggest that homozygous mutation in GJA1 induces a more severe ODDD phenotype, though interfamilial phenotype variability was observed, whereas compound heterozygous mutations in GJA1 cause a mild phenotype.

Sickle cell anemia in Brazil: personal, medical and endodontic patterns.

Sickle cell anemia (SCA) is the most prevalent genetic disease worldwide. Recurrent vaso-occlusive infarcts predispose SCA patients to infections, which are the primary causes of morbidly and mortality. This study aimed to evaluate the relationship between SCA and endodontic diseases. Personal information, medical data (hematological indices, virologic testing, blood transfusions, medications received, splenectomy) and information on the need for endodontic treatment were obtained from SCA patients who were registered and followed up by the Fundação Hemominas, Minas Gerais, Brazil.These data were compared with the need for root canal treatment in SCA patients. One hundred eight patients comprised the studied population, and the rate of the need for endodontic therapy was 10.2%. Among the medical data, a significant difference was observed for eosinophil (p = 0.045) counts and atypical lymphocyte counts (p = 0.036) when the groups (with and without the need for endodontic treatment) were compared. Statistical relevance was observed when comparing the patients with and without the need for root canal therapy concerned eosinophil counts and atypical lymphocyte counts. The differences in statistical medical data, observed between the groups suggest that both parameters are naturally connected to the stimulation of the immune system that can occur in the presence of root canal infections and that can be harmful to SCA individuals.

Sickle cell anemia in Brazil: personal, medical and endodontic patterns

Abstract Sickle cell anemia (SCA) is the most prevalent genetic disease worldwide. Recurrent vaso-occlusive infarcts predispose SCA patients to infections, which are the primary causes of morbidly and mortality. This study aimed to evaluate the relationship between SCA and endodontic diseases. Personal information, medical data (hematological indices, virologic testing, blood transfusions, medications received, splenectomy) and information on the need for endodontic treatment were obtained from SCA patients who were registered and followed up by the Fundação Hemominas, Minas Gerais, Brazil.These data were compared with the need for root canal treatment in SCA patients. One hundred eight patients comprised the studied population, and the rate of the need for endodontic therapy was 10.2%. Among the medical data, a significant difference was observed for eosinophil (p = 0.045) counts and atypical lymphocyte counts (p = 0.036) when the groups (with and without the need for endodontic treatment) were compared. Statistical relevance was observed when comparing the patients with and without the need for root canal therapy concerned eosinophil counts and atypical lymphocyte counts. The differences in statistical medical data, observed between the groups suggest that both parameters are naturally connected to the stimulation of the immune system that can occur in the presence of root canal infections and that can be harmful to SCA individuals.

Periapical cytokine expression in sickle cell disease.

INTRODUCTION: Sickle cell anemia (SCA) is the most prevalent genetic disease worldwide. Patients with SCA exhibit increased levels of proinflammatory mediators as part of a permanently activated immunoinflammatory status. METHODS: The aim of this study was to evaluate the mRNA expression levels of the cytokines interferon (IFN-γ), tumor necrosis factor, interleukin (IL-1ß, IL-17A, IL-10), receptor activator for nuclear factor kappa B ligand, and the chemokines CCL2/MCP-1 and CCL5 in the periapical interstitial fluid from SCA individuals compared with healthy individuals. Samples were collected from 12 teeth of SCA patients and 12 non-SCA patients with apical periodontitis. In addition, 12 teeth were sampled from the periapical region of healthy patients with vital pulp (control). The expression of cytokine mRNA was detected by using real-time polymerase chain reaction. RESULTS: The expression of mRNA for the Th1-associated cytokines IFN-γ, tumor necrosis factor-α, and IL-1ß were significantly higher in SCA individuals than in the control individuals (P < .05). Among Th1-associated cytokines, only IFN-γ was significantly increased in non-SCA compared with control patients (vital pulp). The expression of IL-17A mRNA was significant higher in SCA cases than in control samples (P < .05), whereas the IL-10 mRNA expression was significantly increased in SCA and non-SCA individuals when compared with the control group. Similar levels of receptor activator for nuclear factor kappa B ligand, CCL2, and CCL5 mRNA expression were observed in all samples. However, no significant differences were observed in the expression of cytokine or chemokine mRNA between SCA and non-SCA individuals (P > .05). CONCLUSIONS: The results were able to demonstrate that SCA patients presented prone proinflammatory ability, despite the fact that any differences in periapical immune responses between SCA and non-SCA individuals were not observed.

Cell surface markers for T and B lymphocytes activation and adhesion as putative prognostic biomarkers for head and neck squamous cell carcinoma.

The study population comprised HNSCC patients, risk-positive controls (tabagism and alcoholism habits), and risk-negative controls (without risk factors). Significant increases in the activation status of CD4(+)and CD8(+) T-cells, and higher migration potentials of lymphocytes were observed in HNSCC patients compared with control groups. Although decreased frequency of CD19(+)-B lymphocytes was observed in HSNCC patients, a higher percentage of HLA-DR(+)CD19(+)-B lymphocytes was detected in these individuals as compared with other evaluated groups. Metastasis and tumor grading were the major pathological parameters associated with significant alterations in the expression of activation molecules on circulating CD4(+) and CD8(+) T-cells. A reduced frequency of CD38-expressing CD8(+) T-cells was the most relevant biomarker associated with HNSCC aggressiveness. Performance analysis suggested a cut-off point for the CD8(+)CD38(+)/CD8(+) T-cell ratio of 7.0 for segregating patients according to tumor grading. In contrast, a higher proportion of CD8(+)CD54(+)/CD8(+) T-cells could represent a relevant biomarker associated with metastasis in HNSCC patients, and performance analysis suggested a cut-off point for the CD8(+)CD54(+)/CD8(+) T-cell ratio of 30 for segregating patients according to absence or presence of metastasis. The results obtained can increment immunological aspects of HNSCC and provide tools for the determination of cut-off scores of clinically relevant immunophenotypic prognostic biomarkers.