The natural history and genotype-phenotype correlations of TMPRSS3 hearing loss: an international, multi-center, cohort analysis.

Autor: Colbert BM; Department of Otolaryngology, University of Miami Miller School of Medicine, 1120 NW 14th Street, 5th Floor, Miami, FL, 33136, USA.; Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, USA.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, USA., Lanting C; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands., Smeal M; Department of Otolaryngology, University of Miami Miller School of Medicine, 1120 NW 14th Street, 5th Floor, Miami, FL, 33136, USA., Blanton S; Department of Otolaryngology, University of Miami Miller School of Medicine, 1120 NW 14th Street, 5th Floor, Miami, FL, 33136, USA.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, USA., Dykxhoorn DM; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, USA., Tang PC; Department of Otolaryngology, University of Miami Miller School of Medicine, 1120 NW 14th Street, 5th Floor, Miami, FL, 33136, USA., Getchell RL; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, USA., Velde H; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands., Fehrmann M; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands., Thorpe R; Department of Otolaryngology, University of Iowa, Iowa City, USA., Chapagain P; Department of Physics and Biomolecular Sciences Institute, Florida International University, Miami, USA., Elkhaligy H; Department of Physics and Biomolecular Sciences Institute, Florida International University, Miami, USA., Kremer H; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands., Yntema H; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands., Haer-Wigman L; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands., Redfield S; Boston Children's Hospital, Boston, USA., Sun T; Boston Children's Hospital, Boston, USA., Bruijn S; Amsterdam University Medical Center, Amsterdam, The Netherlands., Plomp A; Amsterdam University Medical Center, Amsterdam, The Netherlands., Goderie T; Amsterdam University Medical Center, Amsterdam, The Netherlands., van de Kamp J; Amsterdam University Medical Center, Amsterdam, The Netherlands., Free RH; Groningen University Medical Center, Groningen, The Netherlands., Wassink-Ruiter JK; Groningen University Medical Center, Groningen, The Netherlands., Widdershoven J; Maastricht University Medical Center, Maastricht, The Netherlands., Vanhoutte E; Maastricht University Medical Center, Maastricht, The Netherlands., Rotteveel L; Leiden University Medical Center, Leiden, The Netherlands., Kriek M; Leiden University Medical Center, Leiden, The Netherlands., van Dooren M; Erasmus Medical Center, Rotterdam, The Netherlands., Hoefsloot L; Erasmus Medical Center, Rotterdam, The Netherlands., de Gier HHW; Erasmus Medical Center, Rotterdam, The Netherlands., Schaefer A; Department of Otolaryngology, University of Iowa, Iowa City, USA., Kolbe D; Department of Otolaryngology, University of Iowa, Iowa City, USA., Azaiez H; Department of Otolaryngology, University of Iowa, Iowa City, USA., Rabie G; Hereditary Research Laboratory and Department of Life Sciences, Bethlehem University, Bethlehem, Palestine., Aburayyan A; University of Washington, Seattle, USA., Kawas M; Hereditary Research Laboratory and Department of Life Sciences, Bethlehem University, Bethlehem, Palestine., Kanaan M; Hereditary Research Laboratory and Department of Life Sciences, Bethlehem University, Bethlehem, Palestine., Holder J; Vanderbilt University, Nashville, USA., Usami SI; Shinshu University School of Medicine, Matsumoto, Japan., Chen Z; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary and Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, USA., Dai P; PLA General Hospital, Beijing, China., Holt J; Boston Children's Hospital, Boston, USA., Nelson R; Department of Otolaryngology, Indiana University School of Medicine, Indianapolis, USA., Choi BY; Seoul National University Bundang Hospital, Seongnam, South Korea., Shearer E; Boston Children's Hospital, Boston, USA., Smith RJH; Department of Otolaryngology, University of Iowa, Iowa City, USA., Pennings R; Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands., Liu XZ; Department of Otolaryngology, University of Miami Miller School of Medicine, 1120 NW 14th Street, 5th Floor, Miami, FL, 33136, USA. xliu@med.miami.edu.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, USA. xliu@med.miami.edu.
Jazyk: angličtina
Zdroj: Human genetics [Hum Genet] 2024 May; Vol. 143 (5), pp. 721-734. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1007/s00439-024-02648-3
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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