Journal article
COCH-related autosomal dominant nonsyndromic hearing loss: a phenotype–genotype study
Human genetics, Vol.141(3-4), pp.889-901
09/16/2021
DOI: 10.1007/s00439-021-02368-y
PMCID: PMC8924011
PMID: 34529116
Abstract
This phenotype–genotype study aimed to investigate the extent of audioprofile variability related to cochlin major domains and to identify potential ethnic-specific differences associated with
COCH
-related hearing loss. Eight Korean families (26 cases) were diagnosed with
COCH
-related hearing loss by exome sequencing. Audiometric test results were combined with those from nine published East Asian families (20 cases) and compared with those from 38 European-descent families (277 cases). Audioprofiles were created by grouping audiometric test results into age ranges by age at testing and then averaging hearing loss thresholds by frequency within age ranges. The functional impact of the identified variants was assessed in vitro by examining the intracellular trafficking, secretion, and cleavage of cochlin. In both East Asian and European-descent families segregating
COCH
-related hearing loss, deafness-associated variants in non-LCCL domains of cochlin were associated with hearing loss that was more severe earlier in life than hearing loss caused by variants in the LCCL domain. Consistent with this phenotypic difference, functional studies demonstrated distinct pathogenic mechanisms for
COCH
variants in a domain-dependent manner; specifically, a cytotoxic effect was observed for the p.Phe230Leu variant, which is located in the vWFA1 domain. No ethnic-specific differences in hearing loss progression were observed, except for those attributable to an overrepresentation of presymptomatic cases in the European-descent cohort.
Details
- Title: Subtitle
- COCH-related autosomal dominant nonsyndromic hearing loss: a phenotype–genotype study
- Creators
- Kyung Seok Oh - Yonsei UniversityDaniel Walls - Roy J. and Lucille A. Carver College of MedicineSun Young Joo - Yonsei UniversityJung Ah Kim - Yonsei UniversityJee Eun Yoo - Yonsei UniversityYoung Ik Koh - Yonsei UniversityDa Hye Kim - Yonsei UniversityJohn Hoon Rim - Yonsei UniversityHye Ji Choi - Yonsei UniversityHye-Youn Kim - Yonsei UniversitySeyoung Yu - Yonsei UniversityRichard J Smith - University of IowaJae Young Choi - Yonsei UniversityHeon Yung Gee - Yonsei UniversityJinsei Jung - Yonsei University
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.141(3-4), pp.889-901
- Publisher
- Springer Berlin Heidelberg
- DOI
- 10.1007/s00439-021-02368-y
- PMID
- 34529116
- PMCID
- PMC8924011
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Grant note
- DC002842; DC012049; DC017955 / national institute on deafness and other communication disorders (http://dx.doi.org/10.13039/100000055) 4845-301; 4851-302; 4851-307 / korea centers for disease control and prevention (http://dx.doi.org/10.13039/501100003669) 6-2021-0003; 6-2021-0002 / yonsei university college of medicine (http://dx.doi.org/10.13039/501100008005) 2019R1A2C1084033; 2020R1A2C3005787; 2021R1A2C2003549; 2018R1A5A2025079 / national research foundation of korea
- Language
- English
- Date published
- 09/16/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984256927302771
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