Genotype-Phenotype Correlations of Pathogenic COCH Variants in DFNA9: A HuGE Systematic Review and Audiometric Meta-Analysis.

Autor: Robijn SMM; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands., Smits JJ; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands.; Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Sezer K; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Huygen PLM; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., Beynon AJ; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., van Wijk E; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands., Kremer H; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands.; Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands., de Vrieze E; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands., Lanting CP; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands., Pennings RJE; Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2022 Jan 27; Vol. 12 (2). Date of Electronic Publication: 2022 Jan 27.
DOI: 10.3390/biom12020220
Abstrakt: Pathogenic missense variants in COCH are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations using the PRISMA and HuGENet guidelines. Study characteristics, risk of bias, genotyping and data on the self-reported age of onset, symptoms of vestibular dysfunction, normative test results for vestibular function, and results of audiovestibular examinations were extracted for each underlying pathogenic COCH variant. The literature search yielded 48 studies describing the audiovestibular phenotypes of 27 DFNA9-associated variants in COCH . Subsequently, meta-analysis of audiometric data was performed by constructing age-related typical audiograms and by performing non-linear regression analyses on the age of onset and progression of hearing loss. Significant differences were found between the calculated ages of onset and progression of the audiovestibular phenotypes of subjects with pathogenic variants affecting either the LCCL domain of cochlin or the vWFA2 and Ivd1 domains. We conclude that the audiovestibular phenotypes associated with DFNA9 are highly variable. Variants affecting the LCCL domain of cochlin generally lead to more progression of hearing loss when compared to variants affecting the other domains. This review serves as a reference for prospective natural history studies in anticipation of mutation-specific therapeutic interventions.
Databáze: MEDLINE
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