| Autor: |
Oh, Kyung Seok, Walls, Daniel, Joo, Sun Young, Kim, Jung Ah, Yoo, Jee Eun, Koh, Young Ik, Kim, Da Hye, Rim, John Hoon, Choi, Hye Ji, Kim, Hye-Youn, Yu, Seyoung, Smith, Richard J., Choi, Jae Young, Gee, Heon Yung, Jung, Jinsei |
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| Zdroj: |
Human Genetics; Apr2022, Vol. 141 Issue 3/4, p889-901, 13p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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