RESUMO
TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype-phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.
Assuntos
Estudos de Associação Genética , Perda Auditiva , Proteínas de Membrana , Serina Endopeptidases , Humanos , Feminino , Masculino , Serina Endopeptidases/genética , Adulto , Proteínas de Membrana/genética , Perda Auditiva/genética , Criança , Pessoa de Meia-Idade , Adolescente , Pré-Escolar , Genótipo , Estudos de Coortes , Fenótipo , Mutação de Sentido Incorreto , Estudos Transversais , Adulto Jovem , Estudos Retrospectivos , Idoso , Proteínas de NeoplasiasRESUMO
OBJECTIVE: To determine whether subjects who have recovered from COVID-19 smell and taste disturbance perform similarly to their COVID-naïve baseline, on gold-standard smell and taste tests. STUDY DESIGN: Prospective cross-sectional study. SETTING: University of Miami Department of Otolaryngology in Miami, FL between September 2021, and August 2022. METHODS: Those previously COVID-19 positive composed the experimental group, those who reported being COVID-naïve composed the control group. Mean total score for the UPSIT Smell Test, and the Burghart Taste Strip test were the primary outcome measures. RESULTS: 70 adult subjects (35 former COVID-positive, 35 COVID-naïve) were enrolled, with 21 females and 14 males in each group. 87 % of all subjects were white and were almost distributed evenly between Hispanic and non-Hispanic. Mean UPSIT total score for the experimental group was 30.6 (95 % CI 28.9-32.3), mean UPSIT total score for the control group was 31.2 (95 % CI 29.7-32.8). Mean Burghart total score for the experimental group was 11.3 (95 % CI 10.6-12.0), mean Burghart total score for the control group was 10.7 (95 % CI 9.7-11.8). These showed a significant overlap of the 95 % CI of the mean total score between the control group and the experimental group, suggesting no significant difference between the two groups. CONCLUSION: These results suggest that COVID-19 patients who experience smell and taste disturbance and recover, regain sensory ability similar to their pre-COVID ability. Further study is needed to validate these findings, but the results are promising in the long-term recovery of COVID-19.