Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss.

BACKGROUND: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL. METHODS: Subjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling. RESULTS: Pathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive. CONCLUSIONS: TECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.

Glucocorticoids suppress NF-kappaB activation induced by LPS and PGN in paranasal sinus epithelial cells.

OBJECTIVES: The aim of this study was to examine the innate immune response induced by toll-like receptors (TLRs) in the paranasal sinus epithelial cells in cell culture models and to examine the effect of glucocorticoids (GCs) on the innate immune response. METHODS: After stimulation with lipopolysaccharide (LPS) and peptidoglycan (PGN), p50 level was measured as an index of the innate response in the paranasal sinus epithelium. To observe the effect of GCs, the specimens were pre-treated with dexamethasone (DEX) for 48 hours prior to stimulation. On immunocytochemistry GR, TLR2 and TLR4 in the paranasal sinus epithelium were observed. RESULTS: The p50 activity levels increased after stimulation with LPS and PGN in a dose-dependent manner. Pretreatment with DEX significantly suppressed the increase in p50 activity levels induced by LPS and PGN. On immunocytochemistry, TLR2 and TLR4 immunoreactivities were relatively high after 48h DEX pretreatment. CONCLUSION: The increase in NF-kappaB activity after LPS and PGN stimulation suggests that stimulation through TLR2 and TLR4 may induce high cytokine expression and inflammatory cell migration in the paranasal sinus epithelial cells. In paranasal sinus epithelial cells GCs not only have anti-inflammatory effects through transcription factor inhibition but also enhance innate host defences.

[Case of NK/T-cell lymphoma of the larynx with hemophagocytic syndrome].

We report the case of a 67-year-old man with NK/T cell lymphoma of the larynx accompanied by hemophagocytic syndrome (HPS) who reported throat paresthesia and was referred for evaluation of a laryngeal tumor extending from the left false vocal cord to the arytenoids. Two separate biopsies from the larynx yielded a histological diagnosis of NK/T-cell lymphoma, nasal and nasal type. Since he showed pancytopenia and remittent fever soon after admission, bone marrow was examined and showed severe hemophagocytosis, leading to a diagnosis of HPS. He died of circulatory and respiratory distresses due to HPS about one month after admission. HPS develops with symptoms of fever, cytopenia, and liver dysfunction, and is characterized by systemic proliferation of benign hemophagocytic histiocytosis in the bone marrow, lymph nodes, liver, and spleen. To the best of our knowledge, this is only the second case of NK/T-cell lymphoma of the larynx with hemophagocytic syndrome to be reported in the Japanese literature.